MADCAM1
protein-codingmucosal vascular addressin cell adhesion molecule 1, the group of Immunoglobulin like domain containing|Ig-like cell adhesion molecule family
Gene summary
The protein encoded by this gene is an endothelial cell adhesion molecule that interacts preferentially with the leukocyte beta7 integrin LPAM-1 (alpha4beta7), L-selectin, and VLA-4 (alpha4beta1) on myeloid cells to direct leukocytes into mucosal and inflamed tissues. It is a member of the immunoglobulin family and is similar to ICAM1 and VCAM1. At least seven alternatively spliced transcripts encoding different protein isoforms have been found for this gene, but the full-length nature of some variants has not been determined. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~16.2 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to MADCAM1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_130760.3. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 3 | 3 | ||||
| missense | 70 | 4 | 74 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 70 | 7 | 0 | 77 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_570116.2 | 5 | MANE Select | |
| Ensembl | ENSP00000215637.2 | 5 | MANE Select | |
| RefSeq | NP_570118.1 | 4 | Standard | |
| Ensembl | ENSP00000304247.2 | 4 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Cell adhesion molecules (CAMs) - Homo sapiens (human)
- Intestinal immune network for IgA production - Homo sapiens (human)
- Integrin cell surface interactions
- Extracellular matrix organization
- Immune System
Biological Process
- positive regulation of leukocyte migration
- immune response
- cell adhesion
- cell-matrix adhesion
- signal transduction
Molecular Function
- integrin binding involved in cell-matrix adhesion
Cellular Component
- plasma membrane
- membrane
- integral component of membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000215637
- Coding exons
- 5
- Length
- 16172
- Individuals with no LoFs
- 121666
- Homozygous LoFs
- 309
- Heterozygous LoFs
- 1674
- Defined
- 123649
- p
- 0.00805
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.476 | 151 | 168 | 0.897 | 0.00000975 | 2320 |
| Missense (PolyPhen) | 19 | 27.868 | 0.68179 | 467 | ||
| Synonymous | -0.370 | 90 | 85.6 | 1.05 | 0.00000580 | 881 |
| Loss of Function | 1.98 | 1 | 6.41 | 0.156 | 2.77e-7 | 108 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.12 | 0.10 | notable |
| Latino/Admixed American | 0.0083 | 0.0077 | notable |
| Ashkenazi Jewish | 0.0021 | 0.00091 | notable |
| East Asian | 0.0028 | 0.0024 | notable |
| Finnish | 0.00082 | 0.00038 | rare |
| European (Non-Finnish) | 0.0010 | 0.00076 | notable |
| South Asian | 0.0023 | 0.0018 | notable |
| Other | 0.0044 | 0.0038 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Cell adhesion leukocyte receptor expressed by mucosal venules, helps to direct lymphocyte traffic into mucosal tissues including the Peyer patches and the intestinal lamina propria. It can bind both integrin alpha-4/beta-7 and L-selectin, regulating both the passage and retention of leukocytes. Isoform 2, lacking the mucin-like domain, may be specialized in supporting integrin alpha-4/beta-7-dependent adhesion strengthening, independent of L- selectin binding.;
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.293
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |