SPIDR
protein-codingscaffold protein involved in DNA repair
Gene summary
Involved in several processes, including cellular response to camptothecin; cellular response to hydroxyurea; and regulation of double-strand break repair. Located in nuclear chromosome and nucleoplasm. Implicated in ovarian dysgenesis 9. [provided by Alliance of Genome Resources, Jul 2025]
- KIAA0146
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~475.4 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0009299
Submitter: Orphanet
Inheritance Pattern: AR
Disease ID:MONDO:0018393
Submitter: King Faisal Specialist Hospital and Research Center
Convincing evidence disputing a role for this gene is this disease has arisen since the initial report identifying an association between the gene and disease. Alhathal et al., 2020 (PMID: 32719396) reported a LOF variant in a large male infertility cohort (n=285 infertile man and case–control fertile man).
Inheritance Pattern: AR
Disease ID:MONDO:0030506
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0030506
Submitter: Ambry Genetics
Inheritance Pattern: Unknown
Disease ID:MONDO:0030506
Submitter: Labcorp Genetics (formerly Invitae)
Clinical Genomic Database (CGD)
Manifestation: Endocrine; Obstetric
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
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to SPIDR variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001080394.4. 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 | 3 | 4 | |||
| missense | 128 | 14 | 2 | 144 | ||
| nonsense | 2 | 2 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 4 | 1 | 6 | ||
| splice donor/acceptor (+/-2bp) | 1 | 6 | 7 | |||
| Total | 4 | 4 | 136 | 17 | 2 | 163 |
Highest pathogenic variant AF is 0.000071867296
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001073863.1 | 20 | MANE Select | |
| Ensembl | ENSP00000297423.4 | 20 | MANE Select | |
| RefSeq | NP_001269845.1 | 18 | Standard | |
| RefSeq | NP_001269848.1 | 18 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- HDR through Homologous Recombination (HR) or Single Strand Annealing (SSA)
- DNA Repair
- DNA Double-Strand Break Repair
- Homology Directed Repair
- Resolution of D-loop Structures through Holliday Junction Intermediates
Biological Process
- double-strand break repair via homologous recombination
- cellular response to DNA damage stimulus
- regulation of double-strand break repair via homologous recombination
- positive regulation of protein complex assembly
- regulation of establishment of protein localization to chromosome
Molecular Function
- protein binding
Cellular Component
- nuclear chromosome
- nucleoplasm
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000297423
- Coding exons
- 20
- Length
- 475702
- Individuals with no LoFs
- 124732
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 103
- Defined
- 124835
- p
- 0.000413
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.217 | 423 | 411 | 1.03 | 0.0000221 | 5902 |
| Missense (PolyPhen) | 86 | 96.833 | 0.88813 | 1476 | ||
| Synonymous | 0.455 | 154 | 161 | 0.954 | 0.00000939 | 1846 |
| Loss of Function | 1.14 | 30 | 37.5 | 0.800 | 0.00000191 | 566 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00052 | 0.00052 | rare |
| Latino/Admixed American | 0.00018 | 0.00017 | rare |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0.00067 | 0.00067 | rare |
| Finnish | 0.000093 | 0.000093 | rare |
| European (Non-Finnish) | 0.00039 | 0.00039 | rare |
| South Asian | 0.00087 | 0.00085 | rare |
| Other | 0.00066 | 0.00066 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Plays a role in DNA double-strand break (DBS) repair via homologous recombination (HR). Serves as a scaffolding protein that helps to promote the recruitment of DNA-processing enzymes like the helicase BLM and recombinase RAD51 to site of DNA damage, and hence contributes to maintain genomic integrity. {ECO:0000269|PubMed:23509288, ECO:0000269|PubMed:23754376}.;
Intolerance Scores
- RVIS EVS
- -0.31
- RVIS percentile EVS
- 32.15
Essentials
- Essential (CRISPR)
- E
- Essential (gene trap)
- H
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |