SPIDR

Summary

SPIDR (scaffold protein involved in DNA repair, HGNC:28971) is a protein-coding gene on chromosome 8q11.21, encoding DNA repair-scaffolding protein (Q14159). Plays a role in DNA double-strand break (DBS) repair via homologous recombination (HR).

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.

Source: NCBI Gene 23514 — RefSeq curated summary.

At a glance

• Gene–disease (curated): ovarian dysgenesis 9 (Moderate, GenCC) — +2 more curated relationships
• GWAS associations: 4
• Clinical variants (ClinVar): 176 total — 4 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 32
• MANE Select transcript: NM_001080394

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28971
Approved symbol	SPIDR
Name	scaffold protein involved in DNA repair
Location	8q11.21
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000164808
Ensembl biotype	protein_coding
OMIM	615384
Entrez	23514

Gene structure

Transcript identifiers

Ensembl transcripts: 30 — 10 protein_coding, 9 protein_coding_CDS_not_defined, 7 nonsense_mediated_decay, 4 retained_intron

ENST00000297423, ENST00000517619, ENST00000517693, ENST00000517824, ENST00000518060, ENST00000518074, ENST00000518692, ENST00000518711, ENST00000519141, ENST00000519362, ENST00000519401, ENST00000519661, ENST00000521214, ENST00000521550, ENST00000521798, ENST00000521918, ENST00000522117, ENST00000522222, ENST00000522321, ENST00000522900, ENST00000523814, ENST00000524006, ENST00000524033, ENST00000524126, ENST00000524141, ENST00000524157, ENST00000541342, ENST00000588781, ENST00000879677, ENST00000936264

RefSeq mRNA: 33 — MANE Select: NM_001080394 NM_001080394, NM_001282916, NM_001282919, NM_001352931, NM_001352932, NM_001352933, NM_001352934, NM_001352935, NM_001352936, NM_001352937, NM_001352938, NM_001352939, NM_001352940, NM_001352941, NM_001352942, NM_001352943, NM_001352944, NM_001352945, NM_001352946, NM_001352947, NM_001352948, NM_001352949, NM_001352950, NM_001352951, NM_001352952, NM_001352953, NM_001352955, NM_001352956, NM_001352957, NM_001352958, NM_001352959, NM_001352960, NM_001352961

CCDS: CCDS43737, CCDS64890, CCDS64891, CCDS87607

Canonical transcript exons

ENST00000297423 — 20 exons

Exon	Start	End
ENSE00002119316	47260938	47260991
ENSE00002138025	47735307	47736306
ENSE00003458396	47279862	47280017
ENSE00003500496	47727200	47727293
ENSE00003511542	47712662	47712872
ENSE00003520636	47291033	47291137
ENSE00003521960	47673801	47673941
ENSE00003525867	47729412	47729465
ENSE00003542845	47598946	47599196
ENSE00003549190	47701956	47702015
ENSE00003550599	47396376	47396626
ENSE00003588736	47700403	47700490
ENSE00003602508	47293867	47294030
ENSE00003611893	47701721	47701864
ENSE00003631131	47713489	47713641
ENSE00003645338	47728933	47729047
ENSE00003653393	47284028	47284094
ENSE00003661939	47407861	47407961
ENSE00003680326	47440323	47440542
ENSE00003688986	47595811	47596006

Expression profiles

Bgee: expression breadth ubiquitous, 285 present calls, max score 97.16.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 27.1920 / max 364.6239, expressed in 1804 samples.

FANTOM5 promoters (15 alternative TSS)

Promoter ID	TPM avg	Samples expressed
88750	23.8642	1802
88749	1.6814	984
88751	0.7686	494
88753	0.6229	97
88748	0.1179	58
88767	0.0473	10
88771	0.0263	7
88754	0.0147	6
88765	0.0110	6
88766	0.0104	3

Top tissues by expression

294 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	97.16	gold quality
right uterine tube	UBERON:0001302	97.09	gold quality
cerebellar hemisphere	UBERON:0002245	96.99	gold quality
right lobe of thyroid gland	UBERON:0001119	96.97	gold quality
tibial nerve	UBERON:0001323	96.95	gold quality
left lobe of thyroid gland	UBERON:0001120	96.76	gold quality
cerebellar cortex	UBERON:0002129	96.66	gold quality
monocyte	CL:0000576	96.63	gold quality
left ovary	UBERON:0002119	96.62	gold quality
endocervix	UBERON:0000458	96.54	gold quality
calcaneal tendon	UBERON:0003701	96.51	gold quality
mononuclear cell	CL:0000842	96.41	gold quality
right lung	UBERON:0002167	96.41	gold quality
right ovary	UBERON:0002118	96.18	gold quality
leukocyte	CL:0000738	95.99	gold quality
ectocervix	UBERON:0012249	95.97	gold quality
minor salivary gland	UBERON:0001830	95.90	gold quality
thyroid gland	UBERON:0002046	95.83	gold quality
body of pancreas	UBERON:0001150	95.71	gold quality
lower esophagus mucosa	UBERON:0035834	95.68	gold quality
upper lobe of left lung	UBERON:0008952	95.51	gold quality
skin of leg	UBERON:0001511	95.42	gold quality
skin of abdomen	UBERON:0001416	95.38	gold quality
adenohypophysis	UBERON:0002196	95.34	gold quality
right frontal lobe	UBERON:0002810	94.93	gold quality
body of uterus	UBERON:0009853	94.90	gold quality
omental fat pad	UBERON:0010414	94.85	gold quality
body of stomach	UBERON:0001161	94.81	gold quality
peritoneum	UBERON:0002358	94.81	gold quality
left uterine tube	UBERON:0001303	94.75	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-119	yes	4.94
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CEBPA

miRNA regulators (miRDB)

47 targeting SPIDR, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-3912-5P	99.95	66.11	925
HSA-MIR-302D-3P	99.89	71.25	1777
HSA-MIR-302A-3P	99.89	71.23	1777
HSA-MIR-302B-3P	99.89	71.23	1777
HSA-MIR-302C-3P	99.89	71.20	1778
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-520E-3P	99.84	70.55	1698
HSA-MIR-373-3P	99.84	70.68	1668
HSA-MIR-372-3P	99.83	70.58	1691
HSA-MIR-520A-3P	99.83	70.59	1687
HSA-MIR-520B-3P	99.83	70.56	1699
HSA-MIR-520C-3P	99.83	70.56	1699
HSA-MIR-520D-3P	99.83	70.78	1676
HSA-MIR-520F-3P	99.82	71.32	1216
HSA-MIR-577	99.78	69.13	2479
HSA-MIR-518A-5P	99.70	69.01	2209
HSA-MIR-527	99.70	69.01	2209
HSA-MIR-6073	99.60	70.36	793
HSA-MIR-548G-3P	99.48	68.67	2159
HSA-MIR-1275	99.47	67.90	2749
HSA-MIR-582-5P	99.47	70.79	2635
HSA-MIR-5009-3P	99.45	69.43	1341
HSA-MIR-6803-5P	99.19	63.90	1026

Literature-anchored findings (GeneRIF, showing 6)

• Consistent with its role as a scaffolding protein for the assembly of BLM and RAD51 foci, cells depleted of SPIDR show increased rate of sister chromatid exchange and defects in homologous recombination repair. (PMID:23509288)
• The FRA8I fragile site includes KIAA0146, CEBPD and PRKDC and may have a role in colorectal cancer (PMID:23603433)
• KIAA0146 is also known as scaffolding protein involved in DNA repair (SPIDR), as a binding partner of FIGNL1 and established that KIAA0146/SPIDR acts with FIGNL1 in homologous recombination repair (PMID:23754376)
• A biallelic mutation in SPIDR may be associated with ovarian dysgenesis in cases of autosomal recessive inheritance. (PMID:27967308)
• our study uncovers a protein complex, which consists of SWS1, SWSAP1, SPIDR and PDS5B, involved in DNA repair and provides insight into Shu complex function and composition. (PMID:31665741)
• A SPIDR homozygous nonsense pathogenic variant in isolated primary ovarian insufficiency with chromosomal instability. (PMID:34697795)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Spidr	ENSMUSG00000041974
rattus_norvegicus	Spidr	ENSRNOG00000037851

Protein

Protein identifiers

DNA repair-scaffolding protein — Q14159 (reviewed: Q14159)

Alternative names: Scaffolding protein involved in DNA repair

All UniProt accessions (12): B3KP42, B4DMX9, Q14159, E5RFY2, E5RGV8, E5RGX8, E5RHG3, E5RIB8, E5RIU7, E5RJJ2, E7EVI9, H0YBC9

UniProt curated annotations — full annotation on UniProt →

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.

Subunit / interactions. Found in a complex, at least composed of BLM, RAD51 and SPIDR; the complex formation is mediated by SPIDR. Interacts (via C-terminal region) with BLM; the interaction is direct. Interacts with RAD51; the interaction is direct. Interacts (via the C-terminal region) with FIGNL1 (via N-terminal one-half region); the interaction is direct.

Subcellular location. Nucleus.

Disease relevance. Ovarian dysgenesis 9 (ODG9) [MIM:619665] An autosomal recessive form of ovarian dysgenesis, a disorder characterized by lack of spontaneous pubertal development, primary amenorrhea, uterine hypoplasia, and hypergonadotropic hypogonadism as a result of streak gonads. The disease is caused by variants affecting the gene represented in this entry.

Induction. Up-regulated in vascular endothelial cells treated with IL4. (Microbial infection) Up-regulated upon SARS-CoV infection.

Isoforms (3)

UniProt ID	Names	Canonical?
Q14159-1	1	yes
Q14159-2	2
Q14159-3	3

RefSeq proteins (33): NP_001073863, NP_001269845, NP_001269848, NP_001339860, NP_001339861, NP_001339862, NP_001339863, NP_001339864, NP_001339865, NP_001339866, NP_001339867, NP_001339868, NP_001339869, NP_001339870, NP_001339871, NP_001339872, NP_001339873, NP_001339874, NP_001339875, NP_001339876, NP_001339877, NP_001339878, NP_001339879, NP_001339880, NP_001339881, NP_001339882, NP_001339884, NP_001339885, NP_001339886, NP_001339887, NP_001339888, NP_001339889, NP_001339890 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR028026	DUF4502	Domain
IPR028032	DUF4503	Domain
IPR053054	DNA_repair-scaffolding	Family

Pfam: PF14950, PF14951

UniProt features (13 total): compositionally biased region 4, region of interest 3, splice variant 3, sequence variant 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q14159-F1	62.19	0.19

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-5693568	Resolution of D-loop Structures through Holliday Junction Intermediates
R-HSA-5685942	HDR through Homologous Recombination (HRR)
R-HSA-5693532	DNA Double-Strand Break Repair
R-HSA-5693537	Resolution of D-Loop Structures
R-HSA-5693538	Homology Directed Repair
R-HSA-5693567	HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA)
R-HSA-73894	DNA Repair

MSigDB gene sets: 206 (showing top): GOBP_REGULATION_OF_DOUBLE_STRAND_BREAK_REPAIR, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_REGULATION_OF_DNA_RECOMBINATION, GOBP_RESPONSE_TO_IONIZING_RADIATION, SHEPARD_CRASH_AND_BURN_MUTANT_UP, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_CHROMOSOME, GOBP_REGULATION_OF_DOUBLE_STRAND_BREAK_REPAIR_VIA_HOMOLOGOUS_RECOMBINATION, GOBP_REGULATION_OF_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_CHROMOSOME, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_ORGANELLE, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_REGULATION_OF_DNA_REPAIR, DOANE_BREAST_CANCER_CLASSES_DN, GOBP_POSITIVE_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_RESPONSE_TO_ALKALOID

GO Biological Process (11): double-strand break repair via homologous recombination (GO:0000724), DNA damage response (GO:0006974), regulation of double-strand break repair via homologous recombination (GO:0010569), positive regulation of protein-containing complex assembly (GO:0031334), regulation of establishment of protein localization to chromosome (GO:0070202), cellular response to ionizing radiation (GO:0071479), cellular response to hydroxyurea (GO:0072711), cellular response to camptothecin (GO:0072757), positive regulation of double-strand break repair (GO:2000781), DNA repair (GO:0006281), DNA recombination (GO:0006310)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (3): nuclear chromosome (GO:0000228), nucleoplasm (GO:0005654), nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Resolution of D-Loop Structures	1
HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA)	1
DNA Repair	1
HDR through Homologous Recombination (HRR)	1
DNA Double-Strand Break Repair	1
Homology Directed Repair	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
double-strand break repair	2
regulation of double-strand break repair	2
DNA metabolic process	2
nuclear lumen	2
recombinational repair	1
cellular response to stress	1
regulation of DNA recombination	1
double-strand break repair via homologous recombination	1
regulation of protein-containing complex assembly	1
positive regulation of cellular component biogenesis	1
positive regulation of cellular component organization	1
protein-containing complex assembly	1
establishment of protein localization to chromosome	1
regulation of establishment of protein localization	1
response to ionizing radiation	1
cellular response to radiation	1
response to hydroxyurea	1
cellular response to nitrogen compound	1
cellular response to alkaloid	1
cellular response to alcohol	1
response to camptothecin	1
positive regulation of DNA repair	1
DNA damage response	1
binding	1
nucleus	1
chromosome	1
cellular anatomical structure	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

578 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SPIDR	SWSAP1	Q6NVH7	753
SPIDR	FIGNL1	Q6PIW4	744
SPIDR	RAD51	Q06609	700
SPIDR	PDS5B	Q9NTI5	598
SPIDR	OR52E4	Q8NGH9	545
SPIDR	MRNIP	Q6NTE8	506
SPIDR	CEBPD	P49716	491
SPIDR	PRKDC	P78527	474
SPIDR	NRDE2	Q9H7Z3	462
SPIDR	UNC79	Q9P2D8	456
SPIDR	ZNF679	Q8IYX0	455
SPIDR	MCM4	P33991	448
SPIDR	POMK	Q9H5K3	444
SPIDR	ZNF331	Q9NQX6	431
SPIDR	HGSNAT	Q68CP4	427

IntAct

37 interactions, top by confidence:

A	B	Type	Score
BLM	TOP3A	psi-mi:“MI:0914”(association)	0.890
SWSAP1	SPIDR	psi-mi:“MI:0915”(physical association)	0.720
SPIDR	SWSAP1	psi-mi:“MI:0915”(physical association)	0.720
SPIDR	SWSAP1	psi-mi:“MI:0914”(association)	0.720
BLM	SPIDR	psi-mi:“MI:0915”(physical association)	0.660
SPIDR	BLM	psi-mi:“MI:0914”(association)	0.660
BLM	SPIDR	psi-mi:“MI:0407”(direct interaction)	0.660
BLM	SPIDR	psi-mi:“MI:0403”(colocalization)	0.660
RAD51	SPIDR	psi-mi:“MI:0915”(physical association)	0.660
RAD51	SPIDR	psi-mi:“MI:0407”(direct interaction)	0.660
SPIDR	BLM	psi-mi:“MI:0915”(physical association)	0.660
SPIDR	RAD51	psi-mi:“MI:0915”(physical association)	0.660
RAD51	SPIDR	psi-mi:“MI:0914”(association)	0.660
ZSWIM7	SPIDR	psi-mi:“MI:0915”(physical association)	0.660
SPIDR	ZSWIM7	psi-mi:“MI:0915”(physical association)	0.660
PLA2G10	CHEK1	psi-mi:“MI:0914”(association)	0.530
SPIDR	FIGNL1	psi-mi:“MI:0915”(physical association)	0.490
FOXL1	DDX39A	psi-mi:“MI:0914”(association)	0.350

BioGRID (37): SPIDR (Affinity Capture-MS), SPIDR (Affinity Capture-MS), SPIDR (Affinity Capture-RNA), SPIDR (Affinity Capture-RNA), SPIDR (Affinity Capture-MS), BLM (Affinity Capture-MS), TOP3A (Affinity Capture-MS), RIF1 (Affinity Capture-MS), RMI1 (Affinity Capture-MS), FIGNL1 (Affinity Capture-MS), FANCM (Affinity Capture-MS), RMI2 (Affinity Capture-MS), BLM (Affinity Capture-Western), SPIDR (Affinity Capture-Western), SPIDR (Reconstituted Complex)

ESM2 similar proteins: A6H5X4, D0QMC3, D2HHP1, G3HKI1, O14862, O35368, P0DOV1, P0DOV2, P41218, P62597, Q05CL8, Q13287, Q13426, Q14159, Q16666, Q4G0J3, Q4R627, Q4R7Q1, Q504N7, Q5I0E2, Q5RAV7, Q5RCV3, Q5RCZ8, Q5RD14, Q60953, Q66JT0, Q68D51, Q6IEE8, Q6K0P9, Q6ZMT9, Q8BGX7, Q8BV49, Q8C0V1, Q8C267, Q8CGE8, Q8IYM2, Q8NAT2, Q8NDB2, Q8NE18, Q8SPH9

Diamond homologs: Q14159, Q8BGX7

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
SPIDR	“form complex”	“SHU complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 16 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Presynaptic phase of homologous DNA pairing and strand exchange	5	113.3×	4e-08

GO biological processes:

GO term	Partners	Fold	FDR
double-strand break repair via homologous recombination	5	52.0×	5e-06
DNA repair	6	25.5×	5e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

176 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	3
Uncertain significance	114
Likely benign	19
Benign	5

Top pathogenic / likely-pathogenic (7)

Variant ID	HGVS	Classification
1255998	NM_001080394.4(SPIDR):c.776+1G>T	Pathogenic
1255999	NM_001080394.4(SPIDR):c.2265del (p.Cys756fs)	Pathogenic
1328490	NM_001080394.4(SPIDR):c.839G>A (p.Trp280Ter)	Pathogenic
1328491	NM_001080394.4(SPIDR):c.814C>T (p.Arg272Ter)	Pathogenic
3780660	NM_001080394.4(SPIDR):c.1727dup (p.Ala577fs)	Likely pathogenic
4277381	NM_001080394.4(SPIDR):c.902_903del (p.Val301fs)	Likely pathogenic
4526335	NM_001080394.4(SPIDR):c.2104dup (p.Cys702fs)	Likely pathogenic

SpliceAI

5789 predictions. Top by Δscore:

Variant	Effect	Δscore
8:47284026:A:AG	acceptor_gain	1.0000
8:47284027:G:GA	acceptor_gain	1.0000
8:47284027:GT:G	acceptor_gain	1.0000
8:47284027:GTC:G	acceptor_gain	1.0000
8:47291030:CA:C	acceptor_loss	1.0000
8:47291031:A:AG	acceptor_gain	1.0000
8:47291031:A:C	acceptor_loss	1.0000
8:47291032:G:GC	acceptor_gain	1.0000
8:47291032:GA:G	acceptor_gain	1.0000
8:47291032:GAA:G	acceptor_gain	1.0000
8:47291032:GAAA:G	acceptor_gain	1.0000
8:47291111:A:G	donor_gain	1.0000
8:47291133:GAGAG:G	donor_gain	1.0000
8:47293862:TTTA:T	acceptor_loss	1.0000
8:47293863:TTA:T	acceptor_loss	1.0000
8:47293865:A:AG	acceptor_gain	1.0000
8:47293865:AGAT:A	acceptor_gain	1.0000
8:47293866:G:GA	acceptor_loss	1.0000
8:47293866:G:GG	acceptor_gain	1.0000
8:47293866:GAT:G	acceptor_gain	1.0000
8:47293866:GATG:G	acceptor_gain	1.0000
8:47293866:GATGA:G	acceptor_gain	1.0000
8:47294028:AAGG:A	donor_loss	1.0000
8:47294032:T:A	donor_loss	1.0000
8:47353837:A:AG	donor_gain	1.0000
8:47353837:A:G	donor_gain	1.0000
8:47394976:A:AG	acceptor_gain	1.0000
8:47394977:G:GG	acceptor_gain	1.0000
8:47394977:GT:G	acceptor_gain	1.0000
8:47396375:GCCAA:G	acceptor_gain	1.0000

AlphaMissense

5934 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:47440541:T:A	W366R	0.995
8:47440541:T:C	W366R	0.995
8:47440476:T:C	F344S	0.992
8:47701980:A:C	S648R	0.991
8:47701982:T:A	S648R	0.991
8:47701982:T:G	S648R	0.991
8:47595819:T:C	L369P	0.990
8:47700416:T:C	F567L	0.989
8:47700418:C:A	F567L	0.989
8:47700418:C:G	F567L	0.989
8:47701983:T:C	F649L	0.989
8:47701985:C:A	F649L	0.989
8:47701985:C:G	F649L	0.989
8:47727247:T:C	C797R	0.989
8:47440388:G:C	A315P	0.988
8:47440524:T:A	V360D	0.988
8:47440530:T:C	I362T	0.988
8:47728995:T:C	L833P	0.988
8:47700437:T:A	W574R	0.985
8:47700437:T:C	W574R	0.985
8:47712849:T:C	F722S	0.985
8:47440394:T:C	C317R	0.984
8:47440530:T:G	I362S	0.984
8:47407899:G:C	R272P	0.983
8:47440389:C:A	A315D	0.983
8:47712771:T:A	V696D	0.983
8:47595852:T:C	L380P	0.982
8:47595866:T:C	C385R	0.982
8:47440347:T:A	V301E	0.981
8:47440530:T:A	I362N	0.981

dbSNP variants (sampled 300 via entrez): RS1000003501 (8:47727133 G>A), RS1000011106 (8:47674951 A>G), RS1000013897 (8:47526322 A>G), RS1000020368 (8:47409680 T>C), RS1000022681 (8:47438382 G>A), RS1000022784 (8:47696600 C>T), RS1000025320 (8:47284961 G>C), RS1000030395 (8:47487738 C>T), RS1000046733 (8:47682744 G>A,T), RS1000052585 (8:47708027 C>T), RS1000057083 (8:47586827 G>A), RS1000061162 (8:47611515 A>G), RS1000071990 (8:47322923 C>T), RS1000079830 (8:47725470 C>T), RS1000087146 (8:47526646 C>G,T)

Disease associations

OMIM: gene MIM:615384 | disease phenotypes: MIM:619665

GenCC curated gene-disease

Disease	Classification	Inheritance
ovarian dysgenesis 9	Moderate	Autosomal recessive
46 XX gonadal dysgenesis	Supportive	Autosomal dominant
male infertility with azoospermia or oligozoospermia due to single gene mutation	Disputed Evidence	Autosomal recessive

Mondo (3): ovarian dysgenesis 9 (MONDO:0030506), 46 XX gonadal dysgenesis (MONDO:0009299), (MONDO:0018393)

Orphanet (1): Rare genetic premature ovarian failure (Orphanet:485382)

HPO phenotypes

32 total (30 of 32 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000013	Hypoplasia of the uterus
HP:0000062	Ambiguous genitalia
HP:0000133	Gonadal dysgenesis
HP:0000144	Decreased fertility
HP:0000252	Microcephaly
HP:0000365	Hearing impairment
HP:0000786	Primary amenorrhea
HP:0000823	Delayed puberty
HP:0000837	Increased circulating gonadotropin level
HP:0000869	Secondary amenorrhea
HP:0000938	Osteopenia
HP:0001166	Arachnodactyly
HP:0001251	Ataxia
HP:0001939	Abnormality of metabolism/homeostasis
HP:0002206	Pulmonary fibrosis
HP:0002225	Sparse pubic hair
HP:0002750	Delayed skeletal maturation
HP:0003621	Juvenile onset
HP:0004322	Short stature
HP:0004349	Reduced bone mineral density
HP:0005625	Osteoporosis of vertebrae
HP:0008209	Premature ovarian insufficiency
HP:0008214	Decreased serum estradiol
HP:0008232	Elevated circulating follicle stimulating hormone level
HP:0008684	Aplasia/hypoplasia of the uterus
HP:0008724	Hypoplasia of the ovary
HP:0009888	Abnormality of secondary sexual hair
HP:0010311	Aplasia/Hypoplasia of the breasts
HP:0010464	Streak ovary

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST001523_36	Visceral adipose tissue adjusted for BMI	4.000000e-06
GCST006979_455	Heel bone mineral density	1.000000e-10
GCST90002393_570	Monocyte count	2.000000e-12
GCST90002394_276	Monocyte percentage of white cells	2.000000e-17

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0009270	heel bone mineral density
EFO:0005091	monocyte count
EFO:0007989	monocyte percentage of leukocytes

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D023961	Gonadal Dysgenesis, 46,XX	C12.050.351.875.253.064.249; C12.050.351.875.253.309.193; C12.200.706.316.064.249; C12.200.706.316.309.193; C12.800.316.064.249; C12.800.316.309.193; C16.131.939.316.064.249; C16.131.939.316.309.193; C19.391.119.064.249; C19.391.119.309.193

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs6473187	SPIDR		0.00	0

CTD chemical–gene interactions

37 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression	3
Aflatoxin B1	affects methylation, decreases expression, decreases methylation	3
sodium arsenite	affects expression, decreases expression	2
Acetaminophen	decreases expression, increases expression	2
Cisplatin	affects expression, increases expression	2
Nickel	increases expression	2
aristolochic acid I	decreases expression	1
FR900359	decreases phosphorylation	1
bisphenol F	affects cotreatment, decreases methylation	1
TAK-243	increases sumoylation	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
bisphenol A	affects cotreatment, increases methylation, decreases methylation	1
beta-lapachone	increases expression	1
arsenite	affects binding, decreases reaction	1
benzo(e)pyrene	decreases methylation, increases methylation	1
aflatoxin B2	decreases methylation	1
methacrylaldehyde	increases oxidation, increases abundance, affects cotreatment	1
di-n-butylphosphoric acid	affects expression	1
abrine	decreases expression	1
bisphenol S	increases methylation, affects cotreatment	1
Decitabine	affects expression	1
Fulvestrant	affects cotreatment, increases methylation, decreases methylation	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Air Pollutants	increases oxidation, affects cotreatment, increases abundance	1
Arsenic	affects methylation	1
Methapyrilene	decreases methylation, increases methylation	1
Ozone	affects cotreatment, increases oxidation, increases abundance	1
Dihydrotestosterone	increases expression	1
Dronabinol	decreases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.