U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

REG4 regenerating family member 4 [ Homo sapiens (human) ]

Gene ID: 83998, updated on 5-Aug-2026
Official Symbol
REG4provided by HGNC
Official Full Name
regenerating family member 4provided by HGNC
Primary source
HGNC:HGNC:22977
See related
Ensembl:ENSG00000134193 MIM:609846; AllianceGenome:HGNC:22977
Gene type
protein coding
RefSeq status
VALIDATED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
GISP; RELP; REG-IV
Summary
Enables heparin binding activity and mannan binding activity. Predicted to act upstream of or within response to bacterium. Located in cytoplasm. [provided by Alliance of Genome Resources, Jul 2025]
Expression
Biased expression in small intestine (RPKM 174.4), colon (RPKM 137.8) and 2 other tissues See more
Orthologs
all
Try the new Gene page
Try the new Transcripts and proteins table
See REG4 in Genome Data Viewer
Location:
1p12
Exon count:
7
Annotation release Status Assembly Chr Location
RS_2025_08 current GRCh38.p14 (GCF_000001405.40) 1 NC_000001.11 (119794017..119811460, complement)
RS_2025_08 current T2T-CHM13v2.0 (GCF_009914755.1) 1 NC_060925.1 (119807250..119824685, complement)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (120336640..120354083, complement)

Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:120254349-120254878 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1598 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 1248 Neighboring gene phosphoglycerate dehydrogenase Neighboring gene 3-hydroxy-3-methylglutaryl-CoA synthase 2 Neighboring gene Sharpr-MPRA regulatory region 1341 Neighboring gene ReSE screen-validated silencer GRCh37_chr1:120323715-120323913 Neighboring gene MPRA-validated peak397 silencer Neighboring gene NBPF member 7, pseudogene Neighboring gene profilin 1 pseudogene 9

Go to nucleotide: Graphics FASTA GenBank

Related articles in PubMed

  1. Reg IV is differently expressed in enteroendocrine cells of human small intestine and colon. Heiskala K, et al. Regul Pept, 2013 May 10. PMID 23499801
  2. Reg IV is a serum biomarker for gastric cancer patients and predicts response to 5-fluorouracil-based chemotherapy. Mitani Y, et al. Oncogene, 2007 Jun 28. PMID 17237819
  3. Expression of the REG IV gene in ulcerative colitis. Nanakin A, et al. Lab Invest, 2007 Mar. PMID 17260007
  4. Reg IV can serve for early diagnosis and therapy. Pankova-Kholmyansky I, et al. Cancer Biol Ther, 2007 Jan. PMID 17297304
  5. Serum concentration of Reg IV in patients with colorectal cancer: overexpression and high serum levels of Reg IV are associated with liver metastasis. Oue N, et al. Oncology, 2007. PMID 18187959

See all (120) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Regenerating gene 4 promotes chemoresistance of colorectal cancer by affecting lipid droplet synthesis and assembly.
    Title: Regenerating gene 4 promotes chemoresistance of colorectal cancer by affecting lipid droplet synthesis and assembly.
  2. The effects of REG4 expression on chemoresistance of ovarian cancer.
    Title: The effects of REG4 expression on chemoresistance of ovarian cancer.
  3. Upregulation of REG IV gene in human intestinal epithelial cells by lipopolysaccharide via downregulation of microRNA-24.
    Title: Upregulation of REG IV gene in human intestinal epithelial cells by lipopolysaccharide via downregulation of microRNA-24.
  4. Reg4 Interacts with CD44 to Regulate Proliferation and Stemness of Colorectal and Pancreatic Cancer Cells.
    Title: Reg4 Interacts with CD44 to Regulate Proliferation and Stemness of Colorectal and Pancreatic Cancer Cells.
  5. Clinicopathological Significance and Prognostic Implications of REG4 Immunohistochemical Expression in Colorectal Cancer.
    Title: Clinicopathological Significance and Prognostic Implications of REG4 Immunohistochemical Expression in Colorectal Cancer.
  6. CDX2 and Reg IV expression and correlation in gastric cancer.
    Title: CDX2 and Reg IV expression and correlation in gastric cancer.
  7. A mutant KRAS-induced factor REG4 promotes cancer stem cell properties via Wnt/beta-catenin signaling.
    Title: A mutant KRAS-induced factor REG4 promotes cancer stem cell properties via Wnt/β-catenin signaling.
  8. The correlation of CDX2 with Reg IV expression was demonstrated in ovarian mucinous carcinoma. Reg IV expression was enhanced by transfection of CDX2 and was suppressed by inhibition of CDX2 expression. OMC-3 cells with ectopically overexpressed CDX2 showed enhanced apoptosis and sensitivity to 5-FU.
    Title: Regulation of REG4 Expression and Prediction of 5-Fluorouracil Sensitivity by CDX2 in Ovarian Mucinous Carcinoma.
  9. REG4 plays an important role in KRAS-driven lung cancer pathogenesis and is a novel biomarker of lung adenocarcinoma subtype. Future studies are required to clarify the underlying mechanisms of REG4 in the division and proliferation of KC tumors and its potential therapeutic value.
    Title: REG4 is an indicator for KRAS mutant lung adenocarcinoma with TTF-1 low expression.
  10. Our study demonstrated that Reg IV positively regulates the expression of SOX9 and is involved in tumor cell invasion and migration in gastric cancer.
    Title: Expression of Reg IV and SOX9 and their correlation in human gastric cancer.
Submit: New GeneRIF Correction See all GeneRIFs (63)

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

Review eQTL and phenotype association data in this region using PheGenI

See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

Products Interactant Other Gene Complex Source Pubs Description

Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
NOT enables calcium ion binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables carbohydrate binding IEA
Inferred from Electronic Annotation
more info
  
enables heparin binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables mannan binding IDA
Inferred from Direct Assay
more info
 PubMed 
Component Evidence Code Pubs
located_in cytoplasm IDA
Inferred from Direct Assay
more info
 PubMed 
is_active_in extracellular region IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in extracellular region IEA
Inferred from Electronic Annotation
more info
  
Preferred Names
regenerating islet-derived protein 4
Names
REG-4
REG-like protein
gastrointestinal secretory protein
reg IV
regenerating gene type IV
regenerating islet-derived family, member 4
regenerating islet-derived protein IV

NEW Try the new Transcript table

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.

mRNA and Protein(s)

  1. NM_001159352.2 → NP_001152824.1  regenerating islet-derived protein 4 isoform 1 precursor

    See identical proteins and their annotated locations for NP_001152824.1

    Status: VALIDATED

    Description
    Transcript Variant: This variant (1) is the longest transcript and encodes the longer isoform (1).
    Source sequence(s)
    AL359752, AY126670
    Consensus CDS
    CCDS906.1
    UniProtKB/Swiss-Prot
    Q8NER6, Q8NER7, Q9BYZ8
    UniProtKB/TrEMBL
    A0ACI8RQX3
    Related
    ENSP00000346158.1, ENST00000354219.6
    Conserved Domains (1) summary
    cd03594
    Location:30 → 156
    CLECT_REG-1_like; C-type lectin-like domain (CTLD) of the type found in Human REG-1 (lithostathine), REG-4, and avian eggshell-specific proteins: ansocalcin, structhiocalcin-1(SCA-1), and -2(SCA-2)

  2. NM_001159353.2 → NP_001152825.1  regenerating islet-derived protein 4 isoform 2 precursor

    See identical proteins and their annotated locations for NP_001152825.1

    Status: VALIDATED

    Description
    Transcript Variant: This variant (3) lacks several 3' exons but has an alternate 3' end, as compared to variant 1. The resulting isoform (2) has a shorter and different C-terminus, as compared to isoform 1.
    Source sequence(s)
    AL359752, AY126672
    Consensus CDS
    CCDS53354.1
    UniProtKB/Swiss-Prot
    Q9BYZ8
    Related
    ENSP00000358409.4, ENST00000369401.4
    Conserved Domains (1) summary
    cl02432
    Location:30 → 55
    CLECT; C-type lectin (CTL)/C-type lectin-like (CTLD) domain

  3. NM_032044.4 → NP_114433.1  regenerating islet-derived protein 4 isoform 1 precursor

    See identical proteins and their annotated locations for NP_114433.1

    Status: VALIDATED

    Description
    Transcript Variant: This variant (2) lacks an exon in the 5' UTR, as compared to variant 1. Variants 1 and 2 encode the same protein (isoform 1).
    Source sequence(s)
    AL359752, AY007243, AY126670
    Consensus CDS
    CCDS906.1
    UniProtKB/Swiss-Prot
    Q8NER6, Q8NER7, Q9BYZ8
    UniProtKB/TrEMBL
    A0ACI8RQX3
    Related
    ENSP00000256585.5, ENST00000256585.10
    Conserved Domains (1) summary
    cd03594
    Location:30 → 156
    CLECT_REG-1_like; C-type lectin-like domain (CTLD) of the type found in Human REG-1 (lithostathine), REG-4, and avian eggshell-specific proteins: ansocalcin, structhiocalcin-1(SCA-1), and -2(SCA-2)

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

  1. NC_000001.11 Reference GRCh38.p14 Primary Assembly

    Range
    119794017..119811460 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060925.1 Alternate T2T-CHM13v2.0

    Range
    119807250..119824685 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q9BYZ8.1 GenPept UniProtKB/Swiss-Prot:Q9BYZ8

Gene LinkOut

The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

Chemical Information
Molecular Biology Databases
Research Materials
Tools