FNDC4
protein-codingfibronectin type III domain containing 4, the group of Fibronectin type III domain containing
Gene summary
Involved in response to transforming growth factor beta. Predicted to be located in endoplasmic reticulum; obsolete extracellular space; and plasma membrane. [provided by Alliance of Genome Resources, Jun 2026]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~3.3 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 FNDC4 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_022823.3. 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 | 0 | |||||
| missense | 14 | 14 | ||||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 17 | 0 | 0 | 17 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_073734.1 | 6 | MANE Select | |
| Ensembl | ENSP00000264703.3 | 6 | MANE Select | |
| Ensembl | ENSP00000604183.1 | 4 | Standard | |
| Ensembl | ENSP00000604183.1 | 4 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- negative regulation of inflammatory response
- response to transforming growth factor beta
Cellular Component
- extracellular region
- extracellular space
- endoplasmic reticulum
- plasma membrane
- integral component of membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000264703
- Coding exons
- 6
- Length
- 3363
- Individuals with no LoFs
- 125739
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 9
- Defined
- 125748
- p
- 0.0000358
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.51 | 94 | 145 | 0.647 | 0.00000892 | 1488 |
| Missense (PolyPhen) | 32 | 49.976 | 0.6403 | 515 | ||
| Synonymous | -0.466 | 60 | 55.6 | 1.08 | 0.00000314 | 504 |
| Loss of Function | 2.84 | 1 | 11.3 | 0.0883 | 6.12e-7 | 114 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.000044 | 0.000044 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Acts as an anti-inflammatory factor in the intestine and colon. Binds to and acts on macrophages to downregulate pro- inflammatory gene expression. Affects key macrophage functions, including phagocytosis, by downregulating many key pathways for macrophage activation, partly via by STAT3 activation and signaling. May be required to dampen the immunological response in colitis. {ECO:0000250|UniProtKB:Q3TR08}.;
Recessive Scores
- pRec
- 0.111
Intolerance Scores
- LoFtool
- 0.271
- RVIS EVS
- -0.19
- RVIS percentile EVS
- 39.68
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.131
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |