CEP131

Summary

CEP131 (centrosomal protein 131, HGNC:29511) is a protein-coding gene on chromosome 17q25.3, encoding Centrosomal protein of 131 kDa (Q9UPN4). Component of centriolar satellites contributing to the building of a complex and dynamic network required to regulate cilia/flagellum formation. It is a selective cancer dependency (DepMap: 47.2% of cell lines).

Enables protein homodimerization activity. Involved in several processes, including intraciliary transport involved in cilium assembly; protein localization to centrosome; and regulation of centrosome duplication. Located in several cellular components, including ciliary transition zone; intercellular bridge; and microtubule organizing center.

Source: NCBI Gene 22994 — RefSeq curated summary.

At a glance

• Gene–disease (curated): male infertility with azoospermia or oligozoospermia due to single gene mutation (Moderate, GenCC)
• GWAS associations: 8
• Clinical variants (ClinVar): 274 total
• Cancer dependency (DepMap): dependent in 47.2% of screened cell lines
• MANE Select transcript: NM_014984

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29511
Approved symbol	CEP131
Name	centrosomal protein 131
Location	17q25.3
Locus type	gene with protein product
Status	Approved
Aliases	AZ1, KIAA1118
Ensembl gene	ENSG00000141577
Ensembl biotype	protein_coding
OMIM	613479
Entrez	22994

Gene structure

Transcript identifiers

Ensembl transcripts: 24 — 23 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000269392, ENST00000374782, ENST00000450824, ENST00000570482, ENST00000570817, ENST00000571292, ENST00000573053, ENST00000575907, ENST00000908009, ENST00000908010, ENST00000908011, ENST00000908012, ENST00000908013, ENST00000908014, ENST00000908015, ENST00000908016, ENST00000908017, ENST00000936461, ENST00000936462, ENST00000936463, ENST00000936464, ENST00000936465, ENST00000971920, ENST00000971921

RefSeq mRNA: 4 — MANE Select: NM_014984 NM_001009811, NM_001319228, NM_001319229, NM_014984

CCDS: CCDS32764, CCDS45808, CCDS82214, CCDS82215

Canonical transcript exons

ENST00000450824 — 26 exons

Exon	Start	End
ENSE00000949885	81192736	81192843
ENSE00000949886	81192476	81192593
ENSE00000949887	81192318	81192392
ENSE00000949888	81191193	81191335
ENSE00001244816	81199381	81199549
ENSE00001244825	81199719	81199835
ENSE00001244854	81206744	81206871
ENSE00001244858	81207125	81207239
ENSE00001244865	81208928	81209022
ENSE00001244870	81219880	81220073
ENSE00001290898	81197712	81197888
ENSE00001294644	81198877	81198971
ENSE00001309735	81193926	81194127
ENSE00001314970	81189915	81189975
ENSE00001316567	81195835	81195951
ENSE00001316674	81196930	81197055
ENSE00001322784	81196701	81196826
ENSE00001325390	81190639	81190802
ENSE00001329283	81194870	81194972
ENSE00001363098	81190907	81191084
ENSE00001464644	81198115	81198297
ENSE00001901943	81189596	81189843
ENSE00003466609	81203494	81203607
ENSE00003549559	81200329	81200446
ENSE00003550668	81202240	81202398
ENSE00003842225	81222769	81222965

Expression profiles

Bgee: expression breadth ubiquitous, 169 present calls, max score 92.30.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.5704 / max 114.5880, expressed in 1742 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
168674	10.4261	1730
168673	0.4603	264
168675	0.2149	76
168672	0.1668	60
168668	0.1192	34
168669	0.0912	30
168670	0.0380	12
168665	0.0188	3
168667	0.0185	4
168666	0.0166	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	92.30	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	90.02	gold quality
tendon of biceps brachii	UBERON:0008188	89.22	gold quality
apex of heart	UBERON:0002098	86.92	gold quality
right testis	UBERON:0004534	86.51	gold quality
left testis	UBERON:0004533	86.46	gold quality
ventricular zone	UBERON:0003053	84.92	gold quality
ganglionic eminence	UBERON:0004023	84.15	gold quality
testis	UBERON:0000473	83.65	gold quality
right hemisphere of cerebellum	UBERON:0014890	83.58	gold quality
adenohypophysis	UBERON:0002196	83.29	gold quality
cerebellar hemisphere	UBERON:0002245	82.90	gold quality
cerebellar cortex	UBERON:0002129	82.68	gold quality
mucosa of transverse colon	UBERON:0004991	82.64	gold quality
right uterine tube	UBERON:0001302	82.62	gold quality
tibial nerve	UBERON:0001323	82.37	gold quality
spleen	UBERON:0002106	82.28	gold quality
endometrium epithelium	UBERON:0004811	82.19	silver quality
olfactory segment of nasal mucosa	UBERON:0005386	81.87	gold quality
body of uterus	UBERON:0009853	81.78	gold quality
lower esophagus mucosa	UBERON:0035834	81.62	gold quality
pituitary gland	UBERON:0000007	81.31	gold quality
cortical plate	UBERON:0005343	80.91	gold quality
cerebellum	UBERON:0002037	80.71	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	80.60	gold quality
right ovary	UBERON:0002118	80.49	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.35	gold quality
left ovary	UBERON:0002119	80.33	gold quality
granulocyte	CL:0000094	80.32	gold quality
heart left ventricle	UBERON:0002084	80.29	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): FOXC1, SP1

miRNA regulators (miRDB)

6 targeting CEP131, 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-4447	99.85	67.81	2900
HSA-MIR-328-5P	99.08	64.65	1000
HSA-MIR-4297	98.77	66.95	2013
HSA-MIR-6885-5P	98.71	64.33	902
HSA-MIR-7156-3P	98.25	67.66	859
HSA-MIR-6849-3P	97.25	64.57	1371

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 47.2% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 8)

• These data therefore highlight the importance of human Cep131 for maintaining genomic integrity (PMID:22797915)
• Analysis of the data suggested that SP1 is a pivotal transcription factor for the regulation of CEP131 expression, consequently leading the control of centrosome functions. (PMID:23137637)
• CEP131 is the key regulatory target of MK2 and 14-3-3 in centriolar satellite remodeling. (PMID:26616734)
• CEP131 serves as a potential prognostic biomarker in HCC (PMID:28694105)
• RNA of AZI1 functions as the “initiator” RNA to induce TMPRSS2-ERG fusion. (PMID:30538195)
• PLK4 phosphorylates CEP131 at Ser-78 to maintain centriolar satellite integrity. (PMID:30804208)
• These findings demonstrate that Cep131 is a novel substrate of Plk4, and that phosphorylation or dysregulated Cep131 overexpression promotes Plk4 stabilization and therefore centrosome amplification, establishing a perspective in understanding a relationship between centrosome amplification and cancer development. (PMID:31358734)
• Hepatic ARID3A facilitates liver cancer malignancy by cooperating with CEP131 to regulate an embryonic stem cell-like gene signature. (PMID:36008383)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	cep131	ENSDARG00000088984
mus_musculus	Cep131	ENSMUSG00000039781
rattus_norvegicus	Cep131	ENSRNOG00000004430
drosophila_melanogaster	dila	FBGN0033447

Protein

Protein identifiers

Centrosomal protein of 131 kDa — Q9UPN4 (reviewed: Q9UPN4)

Alternative names: 5-azacytidine-induced protein 1, Pre-acrosome localization protein 1

All UniProt accessions (5): Q9UPN4, I3L2J8, I3L2X7, I3L316, I3L4M5

UniProt curated annotations — full annotation on UniProt →

Function. Component of centriolar satellites contributing to the building of a complex and dynamic network required to regulate cilia/flagellum formation. In proliferating cells, MIB1-mediated ubiquitination induces its sequestration within centriolar satellites, precluding untimely cilia formation initiation. In contrast, during normal and ultraviolet or heat shock cellular stress-induced ciliogenesis, its non-ubiquitinated form is rapidly displaced from centriolar satellites and recruited to centrosome/basal bodies in a microtubule- and p38 MAPK-dependent manner. Also acts as a negative regulator of BBSome ciliary trafficking. Plays a role in sperm flagellar formation; may be involved in the regulation of intraflagellar transport (IFT) and/or intramanchette (IMT) trafficking, which are important for axoneme extension and/or cargo delivery to the nascent sperm tail. Required for optimal cell proliferation and cell cycle progression; may play a role in the regulation of genome stability in non-ciliogenic cells. Involved in centriole duplication. Required for CEP152, WDR62 and CEP63 centrosomal localization and promotes the centrosomal localization of CDK2. Essential for maintaining proper centriolar satellite integrity.

Subunit / interactions. Self-associates. Associates with the centriolar satellite BBSome protein complex. Interacts with BBS4; the interaction limits BBS4 availability for association with the BBSome complex, and hence negatively regulates ciliary localization of the BBSome complex. Interacts with MIB1. Interacts with PCM1; the interaction increases in response to ultraviolet light (UV) radiation. Associates with microtubules; association with microtubules is reduced in response to cellular stress, such as UV stimulation, in a process that requires p38 MAP kinase signaling. Interacts with CEP290, DCTN1, PCNT, PCM1 and CEP152. Interacts with 14-3-3 proteins following UV-induced phosphorylation by MAPKAPK2; this inhibits formation of novel centriolar satellites. Interacts with SDCCAG8. Interacts with CCDC61. Interacts with PLK4.

Subcellular location. Cytoplasm. Cytoskeleton. Microtubule organizing center. Centrosome. Centriolar satellite. Centriole. Cilium basal body. Cytoplasmic vesicle. Secretory vesicle. Acrosome.

Post-translational modifications. Ubiquitinated. Undergoes monoubiquitination catalyzed by the E3 ubiquitin-protein ligase MIB1 in proliferating cells, preventing cilia formation. Monoubiquitination by MIB1 is inhibited in response to cellular stress, such as ultraviolet light (UV) radiation or heat shock, resulting in cilia formation initiation. MAPKAPK2-dependent phosphorylation at Ser-47 and Ser-78 occurs in response to cellular stress such as exposure to ultraviolet irradiation and promotes binding to 14-3-3 proteins which leads to cytoplasmic sequestration of CEP131 and blocks formation of new centriolar satellites. Phosphorylation at Ser-78 mediated by PLK4 is essential for proper organization and integrity of centriolar satellites but is dispensable for its localization to centrioles and its function in ciliogenesis.

Induction. Up-regulated by the transcription factor SP1.

Miscellaneous. Transient cell cultured-based knock-down (by RNAi) of CEP131 leads to a reduction in ciliogenesis. However, analysis of mice with chronic absence of CEP131 following genetic deletion (knockout) shows that cilia develop and function normally in vivo. This suggests that CEP131 is not essential for ciliogenesis, except for the modified cilia of the developing sperm flagella, and that there is an alternative mechanism to compensate for the lack of CEP131.

Similarity. Belongs to the CEP131 family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9UPN4-1	1	yes
Q9UPN4-2	2
Q9UPN4-3	3

RefSeq proteins (4): NP_001009811, NP_001306157, NP_001306158, NP_055799* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR030465	CEP131	Family

UniProt features (43 total): modified residue 19, compositionally biased region 6, region of interest 5, sequence variant 5, mutagenesis site 4, splice variant 2, chain 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UPN4-F1	67.20	0.33

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 (19): 14, 35, 47, 78, 89, 105, 114, 146, 150, 381, 383, 453, 499, 731, 798, 489, 496, 489, 496

Mutagenesis-validated functional residues (4):

Position	Phenotype
47	partially reduces in vitro phosphorylation by mapkapk2 and decreases binding to 14-3-3. abolishes in vitro phosphorylati
78	partially reduces in vitro phosphorylation by mapkapk2 and decreases binding to 14-3-3. abolishes in vitro phosphorylati
78	phosphomimetic mutant. no effect on its localization to centriole and centriolar satellite or on its function in cilioge
731	no effect on interaction with 14-3-3.

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-2565942	Regulation of PLK1 Activity at G2/M Transition
R-HSA-380259	Loss of Nlp from mitotic centrosomes
R-HSA-380270	Recruitment of mitotic centrosome proteins and complexes
R-HSA-380284	Loss of proteins required for interphase microtubule organization from the centrosome
R-HSA-380320	Recruitment of NuMA to mitotic centrosomes
R-HSA-5620912	Anchoring of the basal body to the plasma membrane
R-HSA-8854518	AURKA Activation by TPX2

MSigDB gene sets: 171 (showing top): GOBP_PROTEIN_LOCALIZATION_TO_CYTOSKELETON, GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOCC_SECRETORY_GRANULE, GOBP_POSITIVE_REGULATION_OF_INTRACELLULAR_PROTEIN_TRANSPORT, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GOBP_MALE_GAMETE_GENERATION, GOCC_MICROTUBULE_ORGANIZING_CENTER, GOBP_POSITIVE_REGULATION_OF_INTRACELLULAR_TRANSPORT, GOBP_CILIUM_ORGANIZATION, GOBP_REGULATION_OF_CELLULAR_LOCALIZATION, GOBP_CILIUM_MOVEMENT, GOBP_REGULATION_OF_CELL_CYCLE, GOCC_CENTROSOME

GO Biological Process (15): sperm axoneme assembly (GO:0007288), positive regulation of cell population proliferation (GO:0008284), regulation of centrosome duplication (GO:0010824), intraciliary transport involved in cilium assembly (GO:0035735), cilium assembly (GO:0060271), protein localization to centrosome (GO:0071539), positive regulation of intracellular protein transport (GO:0090316), manchette assembly (GO:1905198), non-motile cilium assembly (GO:1905515), intramanchette transport (GO:1990953), spermatogenesis (GO:0007283), spermatid development (GO:0007286), cell projection organization (GO:0030030), cell differentiation (GO:0030154), intraciliary transport (GO:0042073)

GO Molecular Function (3): protein homodimerization activity (GO:0042803), protein-containing complex binding (GO:0044877), protein binding (GO:0005515)

GO Cellular Component (16): acrosomal vesicle (GO:0001669), manchette (GO:0002177), centrosome (GO:0005813), centriole (GO:0005814), cytosol (GO:0005829), cilium (GO:0005929), microtubule cytoskeleton (GO:0015630), centriolar satellite (GO:0034451), ciliary transition zone (GO:0035869), ciliary basal body (GO:0036064), intercellular bridge (GO:0045171), sperm head-tail coupling apparatus (GO:0120212), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), cytoplasmic vesicle (GO:0031410), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
G2/M Transition	2
Centrosome maturation	2
Loss of proteins required for interphase microtubule organization from the centrosome	1
Mitotic Prometaphase	1
Assembly of the 9+0 primary cilium	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	8
cilium	3
microtubule organizing center	3
developmental process involved in reproduction	2
axoneme assembly	2
cilium assembly	2
cilium organization	2
spermatid development	2
binding	2
intracellular membraneless organelle	2
cytoplasm	2
sperm flagellum assembly	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
regulation of centrosome cycle	1
centrosome duplication	1
intraciliary transport	1
intraciliary transport involved in cilium assembly	1
protein localization to cilium	1
organelle assembly	1
trans-Golgi to periciliary membrane compartment transport	1
plasma membrane bounded cell projection assembly	1
ciliary transition zone assembly	1
protein localization to microtubule organizing center	1
intracellular protein transport	1
positive regulation of intracellular transport	1
regulation of intracellular protein transport	1
positive regulation of protein transport	1
cellular component assembly	1
manchette	1
protein-containing complex localization	1
protein transport along microtubule	1
male gamete generation	1
germ cell development	1
spermatid differentiation	1
cellular component organization	1
cellular developmental process	1
transport along microtubule	1
identical protein binding	1

Protein interactions and networks

STRING

2027 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CEP131	CEP290	O15078	730
CEP131	CEP72	Q9P209	683
CEP131	PLK4	O00444	666
CEP131	CNTROB	Q8N137	651
CEP131	IFT88	Q13099	632
CEP131	OFD1	O75665	627
CEP131	BBS4	Q96RK4	624
CEP131	CEP170	Q5SW79	621
CEP131	PCNT	O95613	615
CEP131	CCDC14	Q49A88	609
CEP131	PCM1	Q15154	604
CEP131	KIAA0753	Q2KHM9	594
CEP131	CNTRL	Q7Z7A1	573
CEP131	CEP152	O94986	572
CEP131	CEP350	Q5VT06	568

IntAct

191 interactions, top by confidence:

A	B	Type	Score
MED4	MED19	psi-mi:“MI:2364”(proximity)	0.900
CEP290	CCP110	psi-mi:“MI:2364”(proximity)	0.890
PCM1	CEP131	psi-mi:“MI:0915”(physical association)	0.740
CEP131	PCM1	psi-mi:“MI:0915”(physical association)	0.740
DYNLL1	BLTP3B	psi-mi:“MI:0914”(association)	0.730
SLMAP	STRN	psi-mi:“MI:2364”(proximity)	0.710
MAP1LC3B	OFD1	psi-mi:“MI:0914”(association)	0.660
CEP131	CEP290	psi-mi:“MI:0914”(association)	0.650
CEP290	CEP131	psi-mi:“MI:0915”(physical association)	0.650
CEP170	KIF2A	psi-mi:“MI:2364”(proximity)	0.650
PCM1	KIAA0753	psi-mi:“MI:0914”(association)	0.650
YWHAG	BLTP3B	psi-mi:“MI:2364”(proximity)	0.640
LRRC49	EIF3F	psi-mi:“MI:0914”(association)	0.640
YWHAB	BLTP3B	psi-mi:“MI:2364”(proximity)	0.610
YWHAB	BLTP3B	psi-mi:“MI:0914”(association)	0.610
AURKB	SEC16A	psi-mi:“MI:2364”(proximity)	0.570
YWHAH	BLTP3B	psi-mi:“MI:2364”(proximity)	0.570
SAV1	SEC16A	psi-mi:“MI:2364”(proximity)	0.570
CEP104	CCDC66	psi-mi:“MI:2364”(proximity)	0.540
PIBF1	CEP131	psi-mi:“MI:0915”(physical association)	0.530
LTBR	ZNF724	psi-mi:“MI:0914”(association)	0.530
TEX264	PER1	psi-mi:“MI:0914”(association)	0.530
TSSK1B	HSPA8	psi-mi:“MI:0914”(association)	0.530
CLEC11A	VWA8	psi-mi:“MI:0914”(association)	0.530
PNMA2	CCDC85C	psi-mi:“MI:0914”(association)	0.530
TMEM59	B4GALT5	psi-mi:“MI:0914”(association)	0.530
CEP131	CEP152	psi-mi:“MI:0915”(physical association)	0.500

BioGRID (312): CEP131 (Affinity Capture-MS), CEP131 (Affinity Capture-MS), CEP131 (Affinity Capture-MS), CEP131 (Affinity Capture-MS), CEP131 (Affinity Capture-MS), CEP131 (Affinity Capture-MS), CEP131 (Affinity Capture-MS), CEP131 (Affinity Capture-MS), CEP131 (Proximity Label-MS), CEP131 (Proximity Label-MS), CEP131 (Proximity Label-MS), CEP131 (Proximity Label-MS), CEP131 (Proximity Label-MS), CEP131 (Proximity Label-MS), CEP131 (Proximity Label-MS)

ESM2 similar proteins: A0A8I3QA39, A1YB07, A2A6T1, A2A9T0, A2AHG0, A5PKL7, A6NKD9, A7MCY6, B8A5S6, D3ZD05, E1BEQ5, E1U8D0, E9Q6B2, F1MRK3, G3V735, O14529, O60299, O75145, O94964, P60469, Q1LZH7, Q3LUD4, Q3UIL6, Q499E4, Q5JTD0, Q5RCR6, Q5XIA0, Q62036, Q63ZY3, Q6DG50, Q6IQ23, Q6NZT2, Q6PDH0, Q86UU1, Q86X02, Q8BX02, Q8C7U1, Q8IY63, Q8K1Q4, Q8K371

Diamond homologs: A1Z7Z9, Q9UPN4, Q62036, U3JAG9

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
MIB1	down-regulates	CEP131	ubiquitination
MAPKAPK2	“down-regulates quantity”	CEP131	phosphorylation
PLK4	“up-regulates activity”	CEP131	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 196 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
Activation of BAD and translocation to mitochondria	7	45.2×	3e-09
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	7	39.9×	8e-09
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	7	39.9×	8e-09
Activation of BH3-only proteins	7	29.4×	7e-08
Loss of Nlp from mitotic centrosomes	19	25.5×	7e-20
Loss of proteins required for interphase microtubule organization from the centrosome	19	25.5×	7e-20
Anchoring of the basal body to the plasma membrane	26	24.9×	4e-27
AURKA Activation by TPX2	19	24.5×	1e-19

GO biological processes:

GO term	Partners	Fold	FDR
centriole replication	8	35.1×	1e-08
protein localization to centrosome	6	24.2×	3e-05
non-motile cilium assembly	13	22.6×	7e-12
microtubule nucleation	5	18.7×	7e-04
motile cilium assembly	5	17.4×	9e-04
substantia nigra development	7	15.4×	5e-05
mitotic spindle assembly	7	14.4×	7e-05
protein targeting	6	13.2×	7e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	214
Likely benign	22
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

4906 predictions. Top by Δscore:

Variant	Effect	Δscore
17:81189972:CACC:C	acceptor_gain	1.0000
17:81189974:CC:C	acceptor_gain	1.0000
17:81189974:CCCTG:C	acceptor_loss	1.0000
17:81189975:CC:C	acceptor_gain	1.0000
17:81189975:CCTGT:C	acceptor_loss	1.0000
17:81189976:C:CC	acceptor_gain	1.0000
17:81190640:T:TA	donor_gain	1.0000
17:81190651:T:TA	donor_gain	1.0000
17:81190798:TTCAC:T	acceptor_gain	1.0000
17:81190799:TCAC:T	acceptor_gain	1.0000
17:81190800:CAC:C	acceptor_gain	1.0000
17:81190800:CACC:C	acceptor_gain	1.0000
17:81190801:AC:A	acceptor_gain	1.0000
17:81190802:CC:C	acceptor_gain	1.0000
17:81190803:C:CC	acceptor_gain	1.0000
17:81190807:G:C	acceptor_gain	1.0000
17:81190902:CTCA:C	donor_loss	1.0000
17:81190905:A:AC	donor_gain	1.0000
17:81190905:A:AG	donor_loss	1.0000
17:81190905:ACCGC:A	donor_gain	1.0000
17:81190906:C:A	donor_loss	1.0000
17:81190906:C:CC	donor_gain	1.0000
17:81190906:CCG:C	donor_gain	1.0000
17:81190906:CCGCC:C	donor_gain	1.0000
17:81190917:T:TA	donor_gain	1.0000
17:81191080:TGATG:T	acceptor_gain	1.0000
17:81191081:GATG:G	acceptor_gain	1.0000
17:81191081:GATGC:G	acceptor_gain	1.0000
17:81191082:ATG:A	acceptor_gain	1.0000
17:81191082:ATGCT:A	acceptor_gain	1.0000

AlphaMissense

6996 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:81194886:C:A	K704N	0.996
17:81194886:C:G	K704N	0.996
17:81195950:A:G	L637P	0.995
17:81194890:A:G	I703T	0.992
17:81194913:C:A	W695C	0.992
17:81194913:C:G	W695C	0.992
17:81194923:C:G	R692P	0.992
17:81196723:C:G	R629P	0.991
17:81194103:A:G	L718P	0.990
17:81194915:A:G	W695R	0.990
17:81194915:A:T	W695R	0.990
17:81195937:C:A	K641N	0.990
17:81195937:C:G	K641N	0.990
17:81196711:A:G	F633S	0.989
17:81194875:A:T	V708D	0.986
17:81196710:G:C	F633L	0.986
17:81196710:G:T	F633L	0.986
17:81196712:A:G	F633L	0.986
17:81194890:A:C	I703S	0.985
17:81197763:G:C	F535L	0.985
17:81197763:G:T	F535L	0.985
17:81197765:A:G	F535L	0.985
17:81194112:A:G	I715T	0.983
17:81191280:C:G	R896P	0.981
17:81196720:T:G	H630P	0.981
17:81196708:A:T	I634N	0.980
17:81196721:G:C	H630D	0.980
17:81189965:C:G	A1043P	0.979
17:81195938:T:A	K641M	0.979
17:81194112:A:C	I715S	0.978

dbSNP variants (sampled 300 via entrez): RS1000164071 (17:81194645 A>G,T), RS1000269814 (17:81195726 G>A), RS1000356064 (17:81214427 G>T), RS1000415525 (17:81218722 G>A), RS1000534539 (17:81198041 C>A,G,T), RS1000641298 (17:81213302 G>A), RS1000654368 (17:81216704 A>G,T), RS1000707982 (17:81214610 G>A), RS1000714731 (17:81205974 G>A,C), RS1000733198 (17:81208555 G>A,T), RS1000746979 (17:81218008 T>C,G), RS1000802634 (17:81217895 G>A,C), RS1000809006 (17:81201441 AG>A), RS1000859966 (17:81201644 G>A), RS1000899478 (17:81203311 G>A,C)

Disease associations

OMIM: gene MIM:613479 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
male infertility with azoospermia or oligozoospermia due to single gene mutation	Moderate	Autosomal recessive

Mondo (1): (MONDO:0018393)

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST002960_1	Frontotemporal dementia	1.000000e-07
GCST002960_6	Frontotemporal dementia	7.000000e-06
GCST002960_7	Frontotemporal dementia	8.000000e-07
GCST002960_8	Frontotemporal dementia	4.000000e-06
GCST004925_9	IgG N-glycosylation phenotypes (multivariate analysis)	3.000000e-09
GCST004927_7	IgG galactosylation phenotypes (multivariate analysis)	3.000000e-09
GCST004929_7	IgG fucosylation phenotypes (multivariate analysis)	4.000000e-11
GCST009860_8	IgG N-glycosylation phenotypes (multivariate analysis)	1.000000e-15

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0005193	serum IgG glycosylation measurement
EFO:0008425	IgG galactosylation measurement
EFO:0008427	IgG fucosylation measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects binding, increases reaction, increases expression	3
FR900359	affects phosphorylation	1
bisphenol F	affects cotreatment, decreases expression	1
bisphenol A	decreases methylation	1
methylparaben	increases expression	1
benzo(e)pyrene	decreases methylation	1
coumarin	decreases phosphorylation	1
beta-methylcholine	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
perfluoro-n-nonanoic acid	decreases expression	1
abrine	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
Arsenic	affects methylation	1
Benzo(a)pyrene	increases methylation	1
Caffeine	affects phosphorylation	1
Cisplatin	affects cotreatment, increases expression, decreases expression	1
Dexamethasone	affects cotreatment, decreases expression	1
Estradiol	affects cotreatment, decreases expression	1
Indomethacin	decreases expression, affects cotreatment	1
Ivermectin	decreases expression	1
Methapyrilene	decreases methylation	1
Methyl Methanesulfonate	increases expression	1
Progesterone	affects cotreatment, decreases expression	1
Ribonucleotides	affects binding	1
Smoke	decreases expression	1
Thiram	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	increases methylation	1
1-Methyl-3-isobutylxanthine	affects cotreatment, decreases expression	1
Cadmium Chloride	decreases expression	1

Clinical trials (associated diseases)

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