SPIDR

scaffold protein involved in DNA repair

Basic information

Region (hg38): 8:47260877-47736306

Previous symbols: [ "KIAA0146" ]

Links

ENSG00000164808 ∙ NCBI:23514 ∙ OMIM:615384 ∙ HGNC:28971 ∙ Uniprot:Q14159 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• male infertility with azoospermia or oligozoospermia due to single gene mutation (Disputed Evidence), mode of inheritance: AR
• 46 XX gonadal dysgenesis (Supportive), mode of inheritance: AD
• ovarian dysgenesis 9 (Limited), mode of inheritance: AR
• ovarian dysgenesis 9 (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Ovarian dysgenesis 9	AR	General	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	Endocrine; Obstetric	27967308; 34697795

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SPIDR gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SPIDR gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				3		3
missense			51	9	2	62
nonsense						0
start loss						0
frameshift			1			1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				2	2	4
non coding				3	2	5
Total	0	0	52	15	4

Variants in SPIDR

This is a list of pathogenic ClinVar variants found in the SPIDR region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
8-47260965-C-A		not specified	Uncertain significance (Jan 26, 2022)
8-47260972-G-A		not specified	Uncertain significance (Jun 28, 2022)
8-47279863-G-A		not specified	Uncertain significance (Dec 21, 2021)
8-47279925-A-G		not specified	Uncertain significance (Apr 19, 2023)
8-47279949-G-T		not specified	Uncertain significance (Jul 20, 2021)
8-47279959-C-T		not specified	Uncertain significance (Feb 16, 2023)
8-47284040-G-A		not specified	Uncertain significance (Feb 10, 2022)
8-47284050-C-T		not specified	Uncertain significance (May 08, 2023)
8-47284058-G-C		not specified	Uncertain significance (Jul 15, 2021)
8-47284101-A-G			Likely benign (Jan 01, 2024)
8-47291071-A-G		not specified	Uncertain significance (Apr 17, 2023)
8-47291081-G-T		not specified	Uncertain significance (Apr 04, 2023)
8-47291110-G-C		not specified	Uncertain significance (Aug 12, 2021)
8-47293944-G-A		not specified	Uncertain significance (Jan 04, 2022)
8-47394989-G-A		SPIDR-related disorder	Likely benign (May 22, 2023)
8-47396368-T-C			Likely benign (Jan 01, 2024)
8-47396409-G-A		not specified	Uncertain significance (Mar 11, 2024)
8-47396413-G-A		not specified	Uncertain significance (Feb 10, 2022)
8-47396467-A-G		not specified	Uncertain significance (Apr 23, 2024)
8-47396489-A-G			Likely benign (Apr 16, 2018)
8-47396627-G-T		Genetic non-acquired premature ovarian failure	Pathogenic (Oct 01, 2019)
8-47407898-C-T		Ovarian dysgenesis 9	Pathogenic (Feb 16, 2022)
8-47407923-G-A		Ovarian dysgenesis 9	Pathogenic (Dec 16, 2021)
8-47407967-G-A			Benign (May 01, 2024)
8-47440329-A-C			Conflicting classifications of pathogenicity (Jul 01, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SPIDR	protein_coding	protein_coding	ENST00000297423	20	475702

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.38e-17	0.106	124732	0	103	124835	0.000413

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.217	423	411	1.03	0.0000221	5902
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000699	0.000696
Ashkenazi Jewish	0.0000993	0.0000993
East Asian	0.000668	0.000668
Finnish	0.0000928	0.0000928
European (Non-Finnish)	0.000390	0.000388
Middle Eastern	0.000668	0.000668
South Asian	0.000873	0.000850
Other	0.000660	0.000659

dbNSFP

Source: dbNSFP

• 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}.
• Pathway: 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;Resolution of D-Loop Structures;HDR through Homologous Recombination (HRR) (Consensus)

Intolerance Scores

• rvis_EVS: -0.31
• rvis_percentile_EVS: 32.15

Haploinsufficiency Scores

• hipred: N
• hipred_score: 0.123
• ghis: 0.514

Essentials

• essential_gene_CRISPR: E
• essential_gene_gene_trap: H

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Spidr
• Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Gene ontology

• 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;cellular response to ionizing radiation;cellular response to hydroxyurea;cellular response to camptothecin;positive regulation of double-strand break repair
• Cellular component: nuclear chromosome;nucleoplasm
• Molecular function: protein binding