TAF4B

Summary

TAF4B (TATA-box binding protein associated factor 4b, HGNC:11538) is a protein-coding gene on chromosome 18q11.2, encoding Transcription initiation factor TFIID subunit 4B (Q92750). Cell type-specific subunit of the general transcription factor TFIID that may function as a gene-selective coactivator in certain cells.

TATA binding protein (TBP) and TBP-associated factors (TAFs) participate in the formation of the TFIID protein complex, which is involved in initiation of transcription of genes by RNA polymerase II. This gene encodes a cell type-specific TAF that may be responsible for mediating transcription by a subset of activators in B cells. Three transcript variants encoding two different isoforms have been found for this gene.

Source: NCBI Gene 6875 — RefSeq curated summary.

At a glance

• Gene–disease (curated): male infertility with azoospermia or oligozoospermia due to single gene mutation (Supportive, GenCC) — +1 more curated relationship
• GWAS associations: 8
• Clinical variants (ClinVar): 174 total — 1 pathogenic
• Phenotypes (HPO): 14
• MANE Select transcript: NM_005640

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11538
Approved symbol	TAF4B
Name	TATA-box binding protein associated factor 4b
Location	18q11.2
Locus type	gene with protein product
Status	Approved
Aliases	TAFII105
Ensembl gene	ENSG00000141384
Ensembl biotype	protein_coding
OMIM	601689
Entrez	6875

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 8 protein_coding, 1 nonsense_mediated_decay

ENST00000269142, ENST00000418698, ENST00000578121, ENST00000880935, ENST00000880936, ENST00000935352, ENST00000935353, ENST00000935354, ENST00000945498

RefSeq mRNA: 2 — MANE Select: NM_005640 NM_001293725, NM_005640

CCDS: CCDS42421, CCDS77170

Canonical transcript exons

ENST00000269142 — 15 exons

Exon	Start	End
ENSE00000948253	26267516	26267623
ENSE00000948254	26274663	26274824
ENSE00000948255	26274931	26275053
ENSE00001013947	26292246	26292381
ENSE00001135839	26285882	26286499
ENSE00001135846	26281971	26282060
ENSE00001178056	26293426	26293531
ENSE00001279625	26265170	26265315
ENSE00002711117	26226445	26227276
ENSE00002713719	26389845	26391685
ENSE00003479952	26327015	26327140
ENSE00003492044	26335175	26335231
ENSE00003535467	26315229	26315398
ENSE00003675676	26321070	26321200
ENSE00003689643	26357690	26357794

Expression profiles

Bgee: expression breadth ubiquitous, 243 present calls, max score 91.24.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.5671 / max 759.4523, expressed in 1493 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
169767	5.0105	1356
169768	3.2452	844
169769	0.3114	133

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	91.24	gold quality
buccal mucosa cell	CL:0002336	91.24	gold quality
oocyte	CL:0000023	87.36	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.64	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.12	gold quality
Brodmann (1909) area 23	UBERON:0013554	82.75	gold quality
endothelial cell	CL:0000115	79.48	gold quality
middle temporal gyrus	UBERON:0002771	79.14	gold quality
cartilage tissue	UBERON:0002418	77.06	gold quality
calcaneal tendon	UBERON:0003701	76.91	gold quality
tibialis anterior	UBERON:0001385	76.26	silver quality
primary visual cortex	UBERON:0002436	76.04	gold quality
lymph node	UBERON:0000029	75.65	gold quality
tonsil	UBERON:0002372	75.49	gold quality
upper leg skin	UBERON:0004262	75.22	gold quality
tibia	UBERON:0000979	74.98	gold quality
gingival epithelium	UBERON:0001949	74.89	gold quality
esophagus squamous epithelium	UBERON:0006920	74.83	gold quality
mammary duct	UBERON:0001765	74.14	silver quality
ovary	UBERON:0000992	73.89	gold quality
left ovary	UBERON:0002119	73.30	gold quality
gastrocnemius	UBERON:0001388	73.17	gold quality
placenta	UBERON:0001987	72.90	gold quality
postcentral gyrus	UBERON:0002581	72.83	gold quality
gingiva	UBERON:0001828	72.69	gold quality
occipital lobe	UBERON:0002021	72.63	gold quality
muscle of leg	UBERON:0001383	72.56	gold quality
superior frontal gyrus	UBERON:0002661	72.13	gold quality
skin of leg	UBERON:0001511	72.06	gold quality
epithelium of mammary gland	UBERON:0003244	71.94	silver quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.52

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

111 targeting TAF4B, 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-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-3065-5P	99.97	71.56	3281

Literature-anchored findings (GeneRIF, showing 11)

• histone fold domain mediated interaction enhances the DNA binding activity of each of the TAF6-TAF9 and TAF4b-TAF12 pairs and of a histone-like octamer complex composed of the four TAFs (PMID:15601843)
• work suggests that pre-mRNA processing and post-translational modification represent two important regulatory steps for the gonad-specific functions of human TAF(II)105 (PMID:16088961)
• TAF4b incorporation into TFIID induces an open conformation at the lobe involved in TFIIA & putative activator interactions, correlating with differential activator-dependent transcription & promoter recognition by 4b/4-IID. (PMID:18206971)
• Expression of the TAF4b gene is induced by MYC through a non-canonical, but not canonical, E-box which contributes to its specific response to MYC. (PMID:19020761)
• Findings suggest that DNA binding by TAF4/4b-TAF12 facilitates the association of TFIID with the core promoter of a subset of genes. (PMID:19635797)
• We show evidence for the first time of an interdependence of TAF4b and AP-1 family members in cell type-specific promoter recognition and initiation of transcription in the context of cancer progression and EMT. (PMID:20353996)
• Two candidate loci in each family and homozygous truncating mutations p.R611X in TAF4B in family 1 and p.K507Sfs*3 in ZMYND15 in family 2, were identified. (PMID:24431330)
• The existence of a highly conserved TAF4b-dependent gene regulatory network. (PMID:27341508)
• The methionine synthase reductase (MTRR), TAF4B protein, PIWI protein (PIWIL1) four single nucleotide polymorphisms (SNPs) are not shown to be significantly related with non-obstructive azoospermia (NOA). (PMID:30336530)
• Nonobstructive Azoospermia variants included MTRR c.537T>C (rs161870), odds ratios (OR), 3.686, 95% confidence interval (CI), 1.228-11.066; MTRR, c.1049A>G (rs162036), OR, 3.686, 95% CI, 1.228-11.066; PIWIL1, c.1580G>A (rs1106042), OR, 4.737, 95% CI, 1.314-17.072; TAF4B, c.1815T>C (rs1677016), OR, 3.599, 95% CI, 1.255-10.327; and SOX10 c.927T>C (rs139884), OR, 3.192, 95% CI, 1.220-8.353. (PMID:31377750)
• The c.11G>T mutation of the TAF4B gene may be associated with NOA in a Chinese population. (PMID:32502024)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	taf4b	ENSDARG00000075732
mus_musculus	Taf4b	ENSMUSG00000054321
rattus_norvegicus	Taf4b	ENSRNOG00000026023
caenorhabditis_elegans	taf-4	WBGENE00006385

Paralogs (1): TAF4 (ENSG00000130699)

Protein

Protein identifiers

Transcription initiation factor TFIID subunit 4B — Q92750 (reviewed: Q92750)

Alternative names: Transcription initiation factor TFIID 105 kDa subunit

All UniProt accessions (2): Q92750, J3KTH2

UniProt curated annotations — full annotation on UniProt →

Function. Cell type-specific subunit of the general transcription factor TFIID that may function as a gene-selective coactivator in certain cells. TFIID is a multimeric protein complex that plays a central role in mediating promoter responses to various activators and repressors. TAF4B is a transcriptional coactivator of the p65/RELA NF-kappa-B subunit. Involved in the activation of a subset of antiapoptotic genes including TNFAIP3. May be involved in regulating folliculogenesis. Through interaction with OCBA/POU2AF1, acts as a coactivator of B-cell-specific transcription. Plays a role in spermiogenesis and oogenesis.

Subunit / interactions. TFIID is composed of TATA binding protein (TBP) and a number of TBP-associated factors (TAFs). Heterodimerizes with TAF12/TFII20 via the C-terminal H2A-like histone-fold domain. This heterodimer forms a histone-like octamer with the TAF6/TAFII70-TAF9/TAFII31 heterodimer. Interacts with P65/RELA homodimers and P65/RELA-REL heterodimers. Interaction with POU2AF1, via its C-terminal activation domain, is required for octamer-dependent transcription. Interacts with ZNF628.

Subcellular location. Nucleus. Cytoplasm.

Tissue specificity. Preferentially expressed in ovarian granulosa cells (at protein level). Highly expressed in B-cells.

Post-translational modifications. Under stimulation by forskolin, Isoform 1 is phosphorylated by protein kinase A (PKA).

Disease relevance. Spermatogenic failure 13 (SPGF13) [MIM:615841] A disorder resulting in the absence (azoospermia) or reduction (oligozoospermia) of sperm in the semen, leading to male infertility. The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous. May be due to exon inclusion. Unphosphorylated form.

Similarity. Belongs to the TAF4 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q92750-1	1	yes
Q92750-2	2, TAFII105-E9

RefSeq proteins (2): NP_001280654, NP_005631* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003894	TAFH_NHR1	Domain
IPR007900	TAF4_C	Domain
IPR009072	Histone-fold	Homologous_superfamily
IPR037249	TAFH/NHR1_dom_sf	Homologous_superfamily
IPR045144	TAF4	Family

Pfam: PF05236, PF07531

UniProt features (17 total): region of interest 4, domain 2, splice variant 2, sequence variant 2, sequence conflict 2, chain 1, modified residue 1, coiled-coil region 1, short sequence motif 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q92750-F1	56.15	0.20

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 595

Function

Pathways and Gene Ontology

Reactome pathways

20 pathways

ID	Pathway
R-HSA-167161	HIV Transcription Initiation
R-HSA-167162	RNA Polymerase II HIV Promoter Escape
R-HSA-167172	Transcription of the HIV genome
R-HSA-674695	RNA Polymerase II Pre-transcription Events
R-HSA-6804756	Regulation of TP53 Activity through Phosphorylation
R-HSA-73776	RNA Polymerase II Promoter Escape
R-HSA-73779	RNA Polymerase II Transcription Pre-Initiation And Promoter Opening
R-HSA-75953	RNA Polymerase II Transcription Initiation
R-HSA-76042	RNA Polymerase II Transcription Initiation And Promoter Clearance
R-HSA-162587	HIV Life Cycle
R-HSA-162599	Late Phase of HIV Life Cycle
R-HSA-162906	HIV Infection
R-HSA-1643685	Disease
R-HSA-212436	Generic Transcription Pathway
R-HSA-3700989	Transcriptional Regulation by TP53
R-HSA-5633007	Regulation of TP53 Activity
R-HSA-5663205	Infectious disease
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-74160	Gene expression (Transcription)
R-HSA-9824446	Viral Infection Pathways

MSigDB gene sets: 248 (showing top): YAGI_AML_WITH_INV_16_TRANSLOCATION, GOBP_POSITIVE_REGULATION_OF_DNA_TEMPLATED_TRANSCRIPTION_INITIATION, GOBP_OOGENESIS, GOBP_MALE_GAMETE_GENERATION, WEI_MYCN_TARGETS_WITH_E_BOX, REACTOME_HIV_INFECTION, GOBP_REGULATION_OF_DNA_TEMPLATED_TRANSCRIPTION_INITIATION, KEGG_HUNTINGTONS_DISEASE, GOBP_DNA_TEMPLATED_TRANSCRIPTION_INITIATION, GOBP_CELLULAR_PROCESS_INVOLVED_IN_REPRODUCTION_IN_MULTICELLULAR_ORGANISM, GOBP_TRANSCRIPTION_INITIATION_AT_RNA_POLYMERASE_II_PROMOTER, GOBP_MRNA_TRANSCRIPTION, DODD_NASOPHARYNGEAL_CARCINOMA_UP, GOCC_RNA_POLYMERASE_COMPLEX, GOBP_FEMALE_GAMETE_GENERATION

GO Biological Process (9): transcription initiation at RNA polymerase II promoter (GO:0006367), spermatogenesis (GO:0007283), mRNA transcription by RNA polymerase II (GO:0042789), oogenesis (GO:0048477), RNA polymerase II preinitiation complex assembly (GO:0051123), positive regulation of transcription initiation by RNA polymerase II (GO:0060261), DNA-templated transcription (GO:0006351), DNA-templated transcription initiation (GO:0006352), cell differentiation (GO:0030154)

GO Molecular Function (5): DNA binding (GO:0003677), RNA polymerase II general transcription initiation factor activity (GO:0016251), protein heterodimerization activity (GO:0046982), NF-kappaB binding (GO:0051059), RNA polymerase II-specific DNA-binding transcription factor binding (GO:0061629)

GO Cellular Component (5): fibrillar center (GO:0001650), nucleus (GO:0005634), nucleoplasm (GO:0005654), transcription factor TFIID complex (GO:0005669), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-13 pathways:

Category	Pathways
RNA Polymerase II Transcription	4
Transcription of the HIV genome	2
RNA Polymerase II Transcription Initiation And Promoter Clearance	2
Late Phase of HIV Life Cycle	1
Regulation of TP53 Activity	1
HIV Infection	1
HIV Life Cycle	1
Viral Infection Pathways	1
Generic Transcription Pathway	1
Transcriptional Regulation by TP53	1
Disease	1
Gene expression (Transcription)	1
Infectious disease	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transcription by RNA polymerase II	3
cellular anatomical structure	3
transcription initiation at RNA polymerase II promoter	2
RNA biosynthetic process	2
DNA-templated transcription initiation	1
developmental process involved in reproduction	1
male gamete generation	1
mRNA transcription	1
germ cell development	1
female gamete generation	1
transcription preinitiation complex assembly	1
positive regulation of transcription by RNA polymerase II	1
regulation of transcription initiation by RNA polymerase II	1
positive regulation of DNA-templated transcription initiation	1
gene expression	1
DNA-templated transcription	1
cellular developmental process	1
nucleic acid binding	1
general transcription initiation factor activity	1
protein dimerization activity	1
RNA polymerase II-specific DNA-binding transcription factor binding	1
DNA-binding transcription factor binding	1
nucleolus	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
RNA polymerase II, holoenzyme	1
RNA polymerase II transcription regulator complex	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

588 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TAF4B	STRA8	Q7Z7C7	830
TAF4B	TBP	P20226	715
TAF4B	DHRS11	Q6UWP2	650
TAF4B	ZMYND15	Q9H091	634
TAF4B	ZBTB16	Q05516	571
TAF4B	FST	P19883	561
TAF4B	TEX11	Q8IYF3	518
TAF4B	CCND2	P30279	495
TAF4B	CYP19A1	P11511	492
TAF4B	TDRD9	Q8NDG6	482
TAF4B	TAF12	Q16514	435
TAF4B	TBPL2	Q6SJ96	398
TAF4B	TAF5	Q15542	395
TAF4B	BCL6B	Q8N143	372
TAF4B	FIGLA	Q6QHK4	370

IntAct

22 interactions, top by confidence:

A	B	Type	Score
TAF12	TAF4	psi-mi:“MI:0914”(association)	0.760
KPNB1	POM121C	psi-mi:“MI:0914”(association)	0.530
TAF8	TAF4	psi-mi:“MI:0914”(association)	0.530
SPATA25	TAF4	psi-mi:“MI:0914”(association)	0.530
TAF7L	TAF4	psi-mi:“MI:0914”(association)	0.530
BACH1		psi-mi:“MI:0914”(association)	0.350
ILKAP	MYO1C	psi-mi:“MI:0914”(association)	0.350
	TAF4	psi-mi:“MI:0914”(association)	0.350
TAF7L	TAF4	psi-mi:“MI:0914”(association)	0.350
MED26		psi-mi:“MI:0914”(association)	0.350
TBP	BDP1	psi-mi:“MI:0914”(association)	0.350
PRPS2	SMCHD1	psi-mi:“MI:0914”(association)	0.350
TAF4B		psi-mi:“MI:0915”(physical association)	0.000

BioGRID (34): TAF4B (Protein-peptide), TAF4B (Affinity Capture-MS), TAF4B (Affinity Capture-MS), TAF4B (Affinity Capture-MS), TAF4B (Affinity Capture-MS), TAF4B (Affinity Capture-MS), TAF4B (Affinity Capture-Western), TAF4B (Affinity Capture-Western), TAF4B (Affinity Capture-Western), TAF4B (Affinity Capture-MS), TAF4B (Affinity Capture-RNA), TAF4B (Affinity Capture-MS), TAF4B (Affinity Capture-MS), TAF4B (Affinity Capture-MS), TAF4B (Affinity Capture-MS)

ESM2 similar proteins: A0JME2, A5H447, A6NF01, A8CG34, E9Q3G8, F4ID16, G0SDP9, G5E8Z2, O08587, O15504, O88797, O95081, P20676, P49790, P49791, P52591, P52594, P98082, Q03173, Q0VA45, Q2TA45, Q4KLH5, Q5FVW4, Q5PRE5, Q5RB98, Q5SV85, Q5XGN1, Q5ZI22, Q5ZIE8, Q5ZM88, Q64028, Q640Z6, Q6P0U9, Q80WC7, Q86XN7, Q8CIC2, Q8K2K6, Q8K3Z9, Q8L7F7, Q8R080

Diamond homologs: G5E8Z2, O00268, O61707, P47825, Q92750

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 15 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
HIV Transcription Initiation	5	97.1×	2e-08
RNA Polymerase II HIV Promoter Escape	5	97.1×	2e-08
RNA Polymerase II Promoter Escape	5	97.1×	2e-08
RNA Polymerase II Transcription Pre-Initiation And Promoter Opening	5	97.1×	2e-08
RNA Polymerase II Transcription Initiation	5	97.1×	2e-08
RNA Polymerase II Transcription Initiation And Promoter Clearance	5	97.1×	2e-08
Transcription of the HIV genome	5	72.1×	9e-08
Regulation of TP53 Activity through Phosphorylation	6	58.9×	2e-08

GO biological processes:

GO term	Partners	Fold	FDR
transcription initiation at RNA polymerase II promoter	5	124.8×	1e-08
RNA polymerase II preinitiation complex assembly	6	108.7×	8e-10
positive regulation of transcription initiation by RNA polymerase II	5	90.6×	5e-08

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	113
Likely benign	15
Benign	11

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
135657	NM_005640.3(TAF4B):c.1831C>T (p.Arg611Ter)	Pathogenic

SpliceAI

3126 predictions. Top by Δscore:

Variant	Effect	Δscore
18:26265163:A:G	acceptor_gain	1.0000
18:26265165:TATA:T	acceptor_loss	1.0000
18:26265168:A:AG	acceptor_gain	1.0000
18:26265169:G:GG	acceptor_gain	1.0000
18:26265169:G:GT	acceptor_loss	1.0000
18:26267496:T:A	acceptor_gain	1.0000
18:26267507:A:AG	acceptor_gain	1.0000
18:26267507:ACC:A	acceptor_gain	1.0000
18:26267508:C:G	acceptor_gain	1.0000
18:26267509:C:CA	acceptor_gain	1.0000
18:26267624:G:GG	donor_gain	1.0000
18:26273204:G:GT	donor_gain	1.0000
18:26273205:G:T	donor_gain	1.0000
18:26273209:G:GT	donor_gain	1.0000
18:26273209:G:T	donor_gain	1.0000
18:26274660:CAGT:C	acceptor_loss	1.0000
18:26274661:A:AG	acceptor_gain	1.0000
18:26274661:AGTCT:A	acceptor_gain	1.0000
18:26274662:G:GA	acceptor_gain	1.0000
18:26274662:GT:G	acceptor_gain	1.0000
18:26274662:GTC:G	acceptor_gain	1.0000
18:26274662:GTCT:G	acceptor_gain	1.0000
18:26274662:GTCTG:G	acceptor_gain	1.0000
18:26274822:CCG:C	donor_gain	1.0000
18:26274822:CCGGT:C	donor_loss	1.0000
18:26274823:CGGT:C	donor_loss	1.0000
18:26274824:GGTA:G	donor_loss	1.0000
18:26274825:G:C	donor_loss	1.0000
18:26274825:G:GG	donor_gain	1.0000
18:26274826:T:A	donor_loss	1.0000

AlphaMissense

5487 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
18:26281995:T:C	F303L	0.999
18:26281996:T:C	F303S	0.999
18:26281997:T:A	F303L	0.999
18:26281997:T:G	F303L	0.999
18:26282056:T:C	L323P	0.999
18:26274964:T:C	F265L	0.998
18:26274966:C:A	F265L	0.998
18:26274966:C:G	F265L	0.998
18:26275049:T:C	L293P	0.998
18:26282008:T:C	L307P	0.998
18:26282020:T:C	L311P	0.998
18:26282052:T:C	F322L	0.998
18:26282054:T:A	F322L	0.998
18:26282054:T:G	F322L	0.998
18:26282056:T:A	L323H	0.998
18:26335216:G:C	K767N	0.998
18:26335216:G:T	K767N	0.998
18:26335223:G:C	A770P	0.998
18:26357729:G:C	A786P	0.998
18:26357742:C:A	A790D	0.998
18:26357750:G:C	A793P	0.998
18:26357751:C:A	A793D	0.998
18:26274965:T:C	F265S	0.997
18:26274977:T:C	L269S	0.997
18:26282044:T:C	L319P	0.997
18:26357706:T:C	L778P	0.997
18:26357747:G:C	A792P	0.997
18:26274986:T:C	L272P	0.996
18:26282020:T:A	L311H	0.996
18:26282053:T:C	F322S	0.996

dbSNP variants (sampled 300 via entrez): RS1000004948 (18:26251177 C>T), RS1000010973 (18:26296251 A>G), RS1000038124 (18:26281758 A>G), RS1000084163 (18:26296560 T>A), RS1000088342 (18:26281491 T>C), RS1000092521 (18:26339063 C>T), RS1000093738 (18:26366418 T>G), RS1000117374 (18:26389090 A>G), RS1000126371 (18:26366081 C>T), RS1000135420 (18:26266326 G>A), RS1000137638 (18:26233119 C>T), RS1000159227 (18:26319970 A>T), RS1000167590 (18:26342387 C>T), RS1000175933 (18:26361880 T>C), RS1000206313 (18:26342103 T>A)

Disease associations

OMIM: gene MIM:601689 | disease phenotypes: MIM:615841

GenCC curated gene-disease

Disease	Classification	Inheritance
male infertility with azoospermia or oligozoospermia due to single gene mutation	Supportive	Autosomal dominant
spermatogenic failure 13	Limited	Autosomal recessive

Mondo (2): spermatogenic failure 13 (MONDO:0014365), (MONDO:0018393)

Orphanet (0):

HPO phenotypes

14 total (14 of 14 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000027	Azoospermia
HP:0000118	Phenotypic abnormality
HP:0000837	Increased circulating gonadotropin level
HP:0003251	Male infertility
HP:0008232	Elevated circulating follicle stimulating hormone level
HP:0008669	Abnormal spermatogenesis
HP:0008734	Decreased testicular size
HP:0011462	Young adult onset
HP:0011961	Non-obstructive azoospermia
HP:0011962	Obstructive azoospermia
HP:0030087	Abnormal circulating testosterone concentration
HP:0030345	Abnormal circulating luteinizing hormone concentration
HP:0040086	Abnormal prolactin level

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST001523_33	Visceral adipose tissue adjusted for BMI	4.000000e-07
GCST001966_3	Rhegmatogenous retinal detachment	2.000000e-06
GCST007521_4	Asthma-chronic obstructive pulmonary disease overlap syndrome	8.000000e-06
GCST007521_5	Asthma-chronic obstructive pulmonary disease overlap syndrome	8.000000e-06
GCST011354_36	Bell’s palsy	3.000000e-07
GCST011639_8	Cirrhosis (alcohol related)	2.000000e-06
GCST012490_527	Femur bone mineral density x serum urate levels interaction	8.000000e-09
GCST90002403_330	Red blood cell count	2.000000e-10

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0009759	Chronic Obstructive Asthma
EFO:0004531	urate measurement
EFO:0004305	erythrocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
methylmercuric chloride	decreases expression	2
Benzo(a)pyrene	increases expression, increases methylation	2
Cisplatin	affects cotreatment, decreases expression	2
Estradiol	increases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Tretinoin	decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
testosterone enanthate	affects cotreatment, decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases methylation	1
2-methyl-4-isothiazolin-3-one	increases expression	1
trichostatin A	increases expression	1
arsenite	decreases reaction, affects binding	1
potassium chromate(VI)	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
cetrorelix	affects cotreatment, decreases expression	1
monomethylarsonous acid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
ICG 001	decreases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	affects cotreatment, decreases expression	1
gardiquimod	increases expression, decreases reaction	1
Sunitinib	increases expression	1
Fulvestrant	increases methylation	1
Carbamazepine	affects expression	1
Lipopolysaccharides	increases expression, affects response to substance	1
Methotrexate	increases expression	1
Oxazolone	increases expression	1

Clinical trials (associated diseases)

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