CASP9 caspase 9 [ Homo sapiens (human) ]

Gene ID: 842, updated on 14-Sep-2025

Summary

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Official Symbol: CASP9provided by HGNC
Official Full Name: caspase 9provided by HGNC
Primary source: HGNC:HGNC:1511
See related: Ensembl:ENSG00000132906 MIM:602234; AllianceGenome:HGNC:1511
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: MCH6; APAF3; APAF-3; PPP1R56; ICE-LAP6
Summary: This gene encodes a member of the cysteine-aspartic acid protease (caspase) family. Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive proenzymes which undergo proteolytic processing at conserved aspartic residues to produce two subunits, large and small, that dimerize to form the active enzyme. This protein can undergo autoproteolytic processing and activation by the apoptosome, a protein complex of cytochrome c and the apoptotic peptidase activating factor 1; this step is thought to be one of the earliest in the caspase activation cascade. This protein is thought to play a central role in apoptosis and to be a tumor suppressor. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2013]
Expression: Ubiquitous expression in adrenal (RPKM 10.2), ovary (RPKM 6.7) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

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See CASP9 in Genome Data Viewer

Location:: 1p36.21

Exon count:: 11

Annotation release	Status	Assembly	Chr	Location
RS_2025_08	current	GRCh38.p14 (GCF_000001405.40)	1	NC_000001.11 (15491401..15524912, complement)
RS_2025_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	1	NC_060925.1 (14936101..14969610, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	1	NC_000001.10 (15817896..15851285, complement)

Chromosome 1 - NC_000001.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Tissue-specific circular RNA induction during human fetal development
Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
BioProject: PRJNA270632
Publication: PMID 26076956
Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

A Non-Apoptotic Pattern of Caspase-9/Caspase-3 Activation During Differentiation of Human Embryonic Stem Cells into Cardiomyocytes.
Title: A Non-Apoptotic Pattern of Caspase-9/Caspase-3 Activation During Differentiation of Human Embryonic Stem Cells into Cardiomyocytes.
Caspase-9-mediated cleavage of vimentin attenuates the aggressiveness of leukemic NB4 cells.
Title: Caspase-9-mediated cleavage of vimentin attenuates the aggressiveness of leukemic NB4 cells.
GD2-CART01 for Relapsed or Refractory High-Risk Neuroblastoma.
Title: GD2-CART01 for Relapsed or Refractory High-Risk Neuroblastoma.
Association between blood caspase-9 concentrations and septic patient prognosis.
Title: Association between blood caspase-9 concentrations and septic patient prognosis.
The Effect of Caspase 8, 9 Gene Polymorphisms on Non-Hodgkin Lymphoma Susceptibility and Clinical/Pathological Features.
Title: The Effect of Caspase 8, 9 Gene Polymorphisms on Non-Hodgkin Lymphoma Susceptibility and Clinical/Pathological Features.
Caspase 9b Drives Cellular Transformation, Lung Inflammation, and Lung Tumorigenesis.
Title: Caspase 9b Drives Cellular Transformation, Lung Inflammation, and Lung Tumorigenesis.
Correlation between BTG3, CASP9 and LRP4 single-nucleotide polymorphisms and susceptibility to papillary thyroid carcinoma.
Title: Correlation between BTG3, CASP9 and LRP4 single-nucleotide polymorphisms and susceptibility to papillary thyroid carcinoma.
Evaluation of the association between biochemical and immunohistochemical score of caspase-9 and TNFalpha, and the grading of lumbar disc herniation.
Title: Evaluation of the association between biochemical and immunohistochemical score of caspase-9 and TNFα, and the grading of lumbar disc herniation.
Relationship Between CASP9 and CASP10 Gene Polymorphisms and Cancer Susceptibility: Evidence from an Updated Meta-analysis.
Title: Relationship Between CASP9 and CASP10 Gene Polymorphisms and Cancer Susceptibility: Evidence from an Updated Meta-analysis.
C-reactive protein promotes tongue squamous cell carcinoma chemoresistance by inhibiting the activation of caspase-3/9 via the CD64/AKT/mTOR pathway.
Title: C-reactive protein promotes tongue squamous cell carcinoma chemoresistance by inhibiting the activation of caspase-3/9 via the CD64/AKT/mTOR pathway.

Submit: New GeneRIF Correction See all GeneRIFs (261)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Replication interactions

Interaction	Pubs
HIV-1 subtype C activates CASP9, which induces apoptosis of cardiomyocytes and can be inhibited with the HIV-1 neutralizing aptamer UCLA1	PubMed
HIV-1 activates CASP9 (Caspase-9) in CD4+ T lymphocytes as observed in clinical samples collected from HIV-1 infected patients	PubMed

Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	The interaction of cell-associated HIV-1 gp120 with CXCR4-expressing target cells triggers apoptotic processes by activating caspase-9 and -3	PubMed
	env	Treatment of human retinal capillary endothelial cells (HRCECs) with HIV-1 gp120 increases the numbers of apoptotic cells and expression of cleaved caspase-9 protein, but decreases mitochondrial membrane potential	PubMed
	env	Treatment of HIV-1 Env-pseudotyped virus-infected MDM cells with both soluble TRAIL and an agonistic anti-DR5 antibody AD5-10 induces activation of caspase-3, -8, and -9	PubMed
	env	Siva-1 sensitizes CD4-positive T-cells to HIV-1 gp120/gp41-induced apoptosis. The Siva-1-mediated sensitization on CD4-positive T-cells shows significant activation of caspase-3, -8, and -9	PubMed
Envelope transmembrane glycoprotein gp41	env	Siva-1 sensitizes CD4-positive T-cells to HIV-1 gp120/gp41-induced apoptosis. The Siva-1-mediated sensitization on CD4-positive T-cells shows significant activation of caspase-3, -8, and -9	PubMed
Nef	nef	HIV-1 Nef inhibits cleavage of the 45-kDa procaspase-9 to a 35-kDa fragment in BFA-treated MDMs	PubMed
	nef	Microarray analyses have shown HIV-1 Nef-induced upregulation of caspase-9 in primary human brain micro vascular endothelial cells	PubMed
Tat	tat	FasL-induced release of cytochrome c and activation of caspase-9 are inhibited in HIV-1 Tat101-expressing Jurkat cells due to high stability of the mitochondrial inner membrane electrochemical potential	PubMed
	tat	HIV-1 Tat activates caspase 9 to induce apoptotic cell death in retinal pigment epithelial cells	PubMed
	tat	HIV-1 Tat-induced apoptosis through increased expression of anti-apoptotic protein Bcl-2, proapoptotic protein Bax and activation of caspases CASP3 and CASP9 is inhibited by estrogen receptor beta (ER)-mediated estrogen treatment	PubMed
Vpr	vpr	HIV-1 Vpr carboxy-terminally truncated form C81, which does not contain the arginine-rich domain (amino acids 82-96), induces apoptosis via the activation of caspase 9	PubMed
	vpr	Virion-associated Vpr activates caspase 3/7, 8, and 9 in Fas-mediated apoptosis in Jurkat T cells and human activated PBMCs	PubMed
	vpr	Virion-associated Vpr triggers apoptosis through caspases 3/7 and 9 in human T cells independently of other HIV de novo-expressed proteins and also activates caspase 8, the initiator caspase of the death receptor pathway	PubMed
	vpr	Overproduction of EEF2 blocks HIV-1 Vpr-induced cell death both in fission yeast and human cells, suppresses caspase 9 and caspase 3-mediated apoptosis induced by Vpr, and reduces cytochrome c release induced by Vpr	PubMed
	vpr	HIV-1 Vpr-induced apoptosis through caspase activation and Smac release from mitochondria is dependent on G2 cell cycle arrest , but is lost in cells synchronized in G1/S	PubMed
	vpr	HIV-1 Vpr induces apoptosis through activation of caspase 9 as well as by increasing the overall expression level of caspase 9	PubMed
retropepsin	gag-pol	HIV-1 protease directly cleaves and activates procaspase 8 in T cells which is associated with cleavage of BID, mitochondrial release of cytochrome c, activation of the downstream caspases 9 and 3, and cleavage of DFF and PARP	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

SHGC-7118 (e-PCR)
- UniSTS:17174

CASP9_492 (e-PCR)
- UniSTS:277053

G67485 (e-PCR)
- UniSTS:186696

G67486 (e-PCR)
- UniSTS:186697

G67487 (e-PCR)
- UniSTS:186698

G67488 (e-PCR)
- UniSTS:186699

G67489 (e-PCR)
- UniSTS:186700

csnpcasp9-pcr4-1 (e-PCR)
- UniSTS:243023

csnpcasp9-pcr6-1 (e-PCR)
- UniSTS:243024

SHGC-67307 (e-PCR)
- UniSTS:89991

SHGC-36104 (e-PCR)
- UniSTS:17033

SHGC-74255 (e-PCR)
- UniSTS:61340

SHGC-52575 (e-PCR)
- UniSTS:34251

RH67819 (e-PCR)
- UniSTS:30169

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables cysteine-type endopeptidase activity	IBA Inferred from Biological aspect of Ancestor more info
enables cysteine-type endopeptidase activity	IDA Inferred from Direct Assay more info	PubMed
enables cysteine-type endopeptidase activity	IEA Inferred from Electronic Annotation more info
enables cysteine-type endopeptidase activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables cysteine-type endopeptidase activity	TAS Traceable Author Statement more info	PubMed
enables cysteine-type peptidase activity	IEA Inferred from Electronic Annotation more info
enables enzyme activator activity	TAS Traceable Author Statement more info	PubMed
enables hydrolase activity	IEA Inferred from Electronic Annotation more info
enables identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables peptidase activity	IDA Inferred from Direct Assay more info	PubMed
enables peptidase activity	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein kinase binding	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in DNA damage response	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within DNA damage response	IEA Inferred from Electronic Annotation more info
involved_in DNA damage response	IEA Inferred from Electronic Annotation more info
involved_in DNA damage response	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in apoptotic process	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within apoptotic process	IEA Inferred from Electronic Annotation more info
involved_in apoptotic process	IEA Inferred from Electronic Annotation more info
involved_in apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in apoptotic process	TAS Traceable Author Statement more info	PubMed
involved_in cellular response to UV	IDA Inferred from Direct Assay more info	PubMed
involved_in cellular response to dexamethasone stimulus	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within epithelial cell apoptotic process	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within fibroblast apoptotic process	IEA Inferred from Electronic Annotation more info
involved_in glial cell apoptotic process	IEA Inferred from Electronic Annotation more info
involved_in intrinsic apoptotic signaling pathway	IC Inferred by Curator more info	PubMed
involved_in intrinsic apoptotic signaling pathway	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within intrinsic apoptotic signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in intrinsic apoptotic signaling pathway	NAS Non-traceable Author Statement more info	PubMed
involved_in intrinsic apoptotic signaling pathway in response to DNA damage	IBA Inferred from Biological aspect of Ancestor more info
involved_in intrinsic apoptotic signaling pathway in response to DNA damage	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in kidney development	IEA Inferred from Electronic Annotation more info
involved_in leukocyte apoptotic process	IEA Inferred from Electronic Annotation more info
acts_upstream_of neuron apoptotic process	IEA Inferred from Electronic Annotation more info
involved_in platelet formation	TAS Traceable Author Statement more info	PubMed
involved_in positive regulation of apoptotic process	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of execution phase of apoptosis	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of neuron apoptotic process	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within positive regulation of neuron apoptotic process	IEA Inferred from Electronic Annotation more info
involved_in protein maturation	IDA Inferred from Direct Assay more info	PubMed
involved_in protein maturation	IEA Inferred from Electronic Annotation more info
involved_in protein processing	IEA Inferred from Electronic Annotation more info
involved_in proteolysis	IEA Inferred from Electronic Annotation more info
involved_in regulation of apoptotic process	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within response to UV	IEA Inferred from Electronic Annotation more info
involved_in response to UV	IEA Inferred from Electronic Annotation more info
involved_in response to anesthetic	IEA Inferred from Electronic Annotation more info
involved_in response to cobalt ion	IEA Inferred from Electronic Annotation more info
involved_in response to estradiol	IEA Inferred from Electronic Annotation more info
involved_in response to hypoxia	IEA Inferred from Electronic Annotation more info
involved_in response to indole-3-methanol	IEA Inferred from Electronic Annotation more info
involved_in response to ischemia	IEA Inferred from Electronic Annotation more info
involved_in response to lipopolysaccharide	IEA Inferred from Electronic Annotation more info
involved_in signal transduction in response to DNA damage	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
part_of apoptosome	IDA Inferred from Direct Assay more info	PubMed
part_of apoptosome	IPI Inferred from Physical Interaction more info	PubMed
part_of caspase complex	IPI Inferred from Physical Interaction more info	PubMed
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytoplasm	IEA Inferred from Electronic Annotation more info
is_active_in cytosol	IBA Inferred from Biological aspect of Ancestor more info
located_in cytosol	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	IEA Inferred from Electronic Annotation more info
located_in cytosol	TAS Traceable Author Statement more info
is_active_in mitochondrion	IDA Inferred from Direct Assay more info	PubMed
located_in nucleus	IEA Inferred from Electronic Annotation more info
part_of protein-containing complex	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: caspase-9

Names: ICE-like apoptotic protease 6; apoptotic protease MCH-6; apoptotic protease activating factor 3; caspase 9, apoptosis-related cysteine peptidase; protein phosphatase 1, regulatory subunit 56

NP_001220.2

EC 3.4.22.62

NP_001264983.1

EC 3.4.22.62

NP_127463.2

EC 3.4.22.62

XP_005246071.1

EC 3.4.22.62

XP_011540575.1

EC 3.4.22.62

XP_047287990.1

EC 3.4.22.62

XP_054195099.1

EC 3.4.22.62

XP_054195100.1

EC 3.4.22.62

XP_054195101.1

EC 3.4.22.62

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_029188.1 RefSeqGene

Range

5576..38390

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001229.5 → NP_001220.2 caspase-9 isoform alpha precursor

See identical proteins and their annotated locations for NP_001220.2

Status: REVIEWED

Description

Transcript Variant: This variant (alpha) encodes the longest isoform (alpha).

Source sequence(s)

AL512883, BC006463

Consensus CDS

CCDS158.1

UniProtKB/Swiss-Prot

B4E1A3, O95348, P55211, Q53Y70, Q5JRU9, Q5UGI1, Q92852, Q9BQ62, Q9UEQ3, Q9UIJ8

UniProtKB/TrEMBL

A8K7U6

Related

ENSP00000330237.5, ENST00000333868.10

Conserved Domains (2) summary

cd08326
Location:17 → 90

CARD_CASP9; Caspase activation and recruitment domain of Caspase-9

cd00032
Location:152 → 414

CASc; Caspase, interleukin-1 beta converting enzyme (ICE) homologues; Cysteine-dependent aspartate-directed proteases that mediate programmed cell death (apoptosis). Caspases are synthesized as inactive zymogens and activated by proteolysis of the peptide ...
NM_001278054.2 → NP_001264983.1 caspase-9 isoform beta

See identical proteins and their annotated locations for NP_001264983.1

Status: REVIEWED

Description

Transcript Variant: This variant (beta) lacks several alternate in-frame exons in the coding region compared to variant alpha. It encodes isoform beta (also known as caspase-9S, caspase-9 beta, caspase-9b) which is shorter compared to isoform alpha.

Source sequence(s)

AB015653, AL512883

Consensus CDS

CCDS59995.1

UniProtKB/Swiss-Prot

P55211

Related

ENSP00000255256.7, ENST00000348549.9

Conserved Domains (2) summary

cd08326
Location:17 → 90

CARD_CASP9; Caspase activation and recruitment domain of Caspase-9

cl00042
Location:140 → 264

CASc; Caspase, interleukin-1 beta converting enzyme (ICE) homologues; Cysteine-dependent aspartate-directed proteases that mediate programmed cell death (apoptosis). Caspases are synthesized as inactive zymogens and activated by proteolysis of the peptide ...
NM_032996.3 → NP_127463.2 caspase-9 isoform 3

See identical proteins and their annotated locations for NP_127463.2

Status: REVIEWED

Description

Transcript Variant: This variant (3) differs in the 5' UTR, lacks a portion of the 5' coding region, and initiates translation at a downstream start codon, compared to variant alpha. The encoded isoform (3) has a shorter N-terminus, compared to isoform alpha.

Source sequence(s)

AK303743, AL512883, DA078665

Consensus CDS

CCDS159.2

UniProtKB/TrEMBL

A8K7R5, A8K7U6

Related

ENSP00000365051.4, ENST00000375890.8

Conserved Domains (1) summary

cd00032
Location:69 → 331

CASc; Caspase, interleukin-1 beta converting enzyme (ICE) homologues; Cysteine-dependent aspartate-directed proteases that mediate programmed cell death (apoptosis). Caspases are synthesized as inactive zymogens and activated by proteolysis of the peptide ...

RNA

NR_102732.2 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (4) uses an alternate splice site in an internal exon compared to variant 1. This variant is represented as non-coding because the use of the 5'-most supported translational start codon, as used in variant alpha, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

AL512883, AY732490, HY027003
NR_102733.2 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (5) uses an alternate splice site in an internal exon compared to variant 1. This variant is represented as non-coding because the use of the 5'-most supported translational start codon, as used in variant alpha, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

AJ781267, AL512883

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2025_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000001.11 Reference GRCh38.p14 Primary Assembly

Range

15491401..15524912 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_005246014.3 → XP_005246071.1 caspase-9 isoform X1

See identical proteins and their annotated locations for XP_005246071.1

UniProtKB/TrEMBL

A8K7R5, A8K7U6

Conserved Domains (1) summary

cd00032
Location:69 → 331

CASc; Caspase, interleukin-1 beta converting enzyme (ICE) homologues; Cysteine-dependent aspartate-directed proteases that mediate programmed cell death (apoptosis). Caspases are synthesized as inactive zymogens and activated by proteolysis of the peptide ...
XM_047432034.1 → XP_047287990.1 caspase-9 isoform X2
XM_011542273.4 → XP_011540575.1 caspase-9 isoform X3

UniProtKB/TrEMBL

F8VVS7, Q59GG2

Related

ENSP00000449584.1, ENST00000546424.5

Conserved Domains (2) summary

cd08326
Location:17 → 90

CARD_CASP9; Caspase activation and recruitment domain of Caspase-9

cd00032
Location:152 → 397

CASc; Caspase, interleukin-1 beta converting enzyme (ICE) homologues; Cysteine-dependent aspartate-directed proteases that mediate programmed cell death (apoptosis). Caspases are synthesized as inactive zymogens and activated by proteolysis of the peptide ...