SRRM4
protein-codingserine/arginine repetitive matrix 4
Gene summary
SRRM4 promotes alternative splicing and inclusion of neural-specific exons in target mRNAs (Calarco et al., 2009 [PubMed 19737518]).[supplied by OMIM, Oct 2009]
- KIAA1853
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~181.5 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 SRRM4 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_194286.4. 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 | 1 | 1 | ||||
| missense | 92 | 4 | 96 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 94 | 4 | 0 | 98 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_919262.2 | 13 | MANE Select | |
| Ensembl | ENSP00000267260.4 | 13 | MANE Select | |
| Ensembl | ENSP00000493188.1 | 3 | Standard | |
| Ensembl | ENSP00000572329.1 | 12 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| srrm4 | Danio rerio | Structure: ventricular system Quality: increased volume abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- regulation of alternative mRNA splicing, via spliceosome
- mRNA processing
- nervous system development
- sensory perception of sound
- RNA splicing
Molecular Function
- mRNA binding
Cellular Component
- nucleus
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000267260
- Coding exons
- 13
- Length
- 181557
- Individuals with no LoFs
- 124630
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 11
- Defined
- 124641
- p
- 0.0000441
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.39 | 311 | 388 | 0.801 | 0.0000262 | 3885 |
| Missense (PolyPhen) | 71 | 99.047 | 0.71683 | 951 | ||
| Synonymous | 0.209 | 141 | 144 | 0.978 | 0.00000794 | 1252 |
| Loss of Function | 4.10 | 7 | 32.0 | 0.218 | 0.00000203 | 350 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000065 | 0.000065 | rare |
| Latino/Admixed American | 0.000030 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00011 | 0.00011 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000054 | 0.000053 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Splicing factor specifically required for neural cell differentiation. Acts in conjunction with nPTB/PTBP2 by binding directly to its regulated target transcripts and promotes neural- specific exon inclusion in many genes that function in neural cell differentiation. Required to promote the inclusion of neural- specific exon 10 in nPTB/PTBP2, leading to increased expression of neural-specific nPTB/PTBP2. Also promotes the inclusion of exon 16 in DAAM1 in neuron extracts. Promotes alternative splicing of REST transcripts to produce a REST isoform (REST4) with greatly reduced repressive activity, thereby activating expression of REST targets in neural cells. Plays an important role during embryonic development as well as in the proper functioning of the adult nervous system. Regulates alternative splicing events in genes with important neuronal functions (By similarity). {ECO:0000250|UniProtKB:Q8BKA3}.;
Recessive Scores
- pRec
- 0.109
Intolerance Scores
- LoFtool
- 0.534
- RVIS EVS
- 0.11
- RVIS percentile EVS
- 62.1
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.731
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | High |
| Cancer | Medium | Medium | Medium |