SSR4
protein-codingsignal sequence receptor subunit 4
Gene summary
This gene encodes the delta subunit of the translocon-associated protein complex which is involved in translocating proteins across the endoplasmic reticulum membrane. The encoded protein is located in the Xq28 region and is arranged in a compact head-to-head manner with the isocitrate dehydrogenase 3 (NAD+) gamma gene and both genes are driven by a CpG-embedded bidirectional promoter. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Mar 2011]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~5.0 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: XL
Disease ID:MONDO:0010490
Submitter: Orphanet
Inheritance Pattern: XL
Disease ID:MONDO:0010490
Submitter: Ambry Genetics
Inheritance Pattern: XL
Disease ID:MONDO:0010490
Submitter: PanelApp Australia
Inheritance Pattern: XL
Disease ID:MONDO:0010490
Submitter: Labcorp Genetics (formerly Invitae)
Clinical Genomic Database (CGD)
Manifestation: Biochemical; Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic
Intervention: General
Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing
Comments: Hepatic-metabolized agents should be avoided
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to SSR4 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_006280.3. 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 | 9 | 20 | 1 | 30 | ||
| missense | 62 | 2 | 1 | 65 | ||
| nonsense | 4 | 1 | 2 | 7 | ||
| start loss | 0 | |||||
| frameshift | 2 | 2 | 4 | |||
| splice donor/acceptor (+/-2bp) | 5 | 3 | 12 | 20 | ||
| Total | 11 | 6 | 85 | 22 | 2 | 126 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_006271.1 | 6 | MANE Select | |
| Ensembl | ENSP00000359103.3 | 6 | MANE Select | |
| RefSeq | NP_001191455.1 | 7 | Standard | |
| RefSeq | NP_001191456.1 | 7 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| ssr4 | Danio rerio | Structure: post-vent region Quality: curved abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Protein processing in endoplasmic reticulum - Homo sapiens (human)
- SRP-dependent cotranslational protein targeting to membrane
- Translation
- Metabolism of proteins
Cellular Component
- Sec61 translocon complex
- integral component of membrane
- extracellular exosome
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000320857
- Coding exons
- 6
- Length
- 4990
- Individuals with no LoFs
- 0
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 0
- Defined
- 0
- p
- 0.00
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.902 | 55 | 77.3 | 0.711 | 0.00000645 | 1119 |
| Missense (PolyPhen) | 15 | 30.234 | 0.49613 | 458 | ||
| Synonymous | -1.18 | 45 | 36.0 | 1.25 | 0.00000345 | 349 |
| Loss of Function | 2.41 | 0 | 6.78 | 0.00 | 4.86e-7 | 105 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0 | 0.0 | absent |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: TRAP proteins are part of a complex whose function is to bind calcium to the ER membrane and thereby regulate the retention of ER resident proteins.;
- Disease
- DISEASE: Congenital disorder of glycosylation 1Y (CDG1Y) [MIM:300934]: A form of congenital disorder of glycosylation, a multisystem disorder caused by a defect in glycoprotein biosynthesis and characterized by under-glycosylated serum glycoproteins. Congenital disorders of glycosylation result in a wide variety of clinical features, such as defects in the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. The broad spectrum of features reflects the critical role of N-glycoproteins during embryonic development, differentiation, and maintenance of cell functions. {ECO:0000269|PubMed:24218363}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.446
Intolerance Scores
- RVIS EVS
- 0.01
- RVIS percentile EVS
- 54.63
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.801
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |