ANAPC10

Summary

ANAPC10 (anaphase promoting complex subunit 10, HGNC:24077) is a protein-coding gene on chromosome 4q31.21, encoding Anaphase-promoting complex subunit 10 (Q9UM13). Component of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin ligase that controls progression through mitosis and the G1 phase of the cell cycle. It is a common-essential gene (DepMap: required in 98.2% of cancer cell lines).

ANAPC10 is a core subunit of the anaphase-promoting complex (APC), or cyclosome, a ubiquitin protein ligase that is essential for progression through the cell cycle. APC initiates sister chromatid separation by ubiquitinating the anaphase inhibitor securin (PTTG1; MIM 604147) and triggers exit from mitosis by ubiquitinating cyclin B (CCNB1; MIM 123836), the activating subunit of cyclin-dependent kinase-1 (CDK1; MIM 116940) (summary by Wendt et al., 2001 [PubMed 11524682]).

Source: NCBI Gene 10393 — RefSeq curated summary.

At a glance

• GWAS associations: 49
• Clinical variants (ClinVar): 30 total — 1 pathogenic
• Cancer dependency (DepMap): dependent in 98.2% of screened cell lines (common-essential)
• MANE Select transcript: NM_001256706

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24077
Approved symbol	ANAPC10
Name	anaphase promoting complex subunit 10
Location	4q31.21
Locus type	gene with protein product
Status	Approved
Aliases	APC10, DOC1, DKFZP564L0562
Ensembl gene	ENSG00000164162
Ensembl biotype	protein_coding
OMIM	613745
Entrez	10393

Gene structure

Transcript identifiers

Ensembl transcripts: 34 — 25 protein_coding, 6 protein_coding_CDS_not_defined, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000309439, ENST00000451299, ENST00000502562, ENST00000502651, ENST00000502847, ENST00000504721, ENST00000506851, ENST00000507134, ENST00000507656, ENST00000508087, ENST00000510270, ENST00000511466, ENST00000512680, ENST00000513054, ENST00000514390, ENST00000514704, ENST00000613466, ENST00000641499, ENST00000877447, ENST00000877448, ENST00000877449, ENST00000877450, ENST00000914513, ENST00000914514, ENST00000914515, ENST00000914516, ENST00000914517, ENST00000914518, ENST00000914519, ENST00000914520, ENST00000914521, ENST00000914522, ENST00000914523, ENST00000914524

RefSeq mRNA: 9 — MANE Select: NM_001256706 NM_001256706, NM_001256707, NM_001256708, NM_001256709, NM_001256710, NM_001256711, NM_001256712, NM_001318367, NM_014885

CCDS: CCDS43273

Canonical transcript exons

ENST00000507656 — 5 exons

Exon	Start	End
ENSE00002063905	144994576	144995603
ENSE00002072037	145098120	145098196
ENSE00003675844	145095985	145096111
ENSE00003787012	145064572	145064692
ENSE00003790581	145081660	145081750

Expression profiles

Bgee: expression breadth ubiquitous, 282 present calls, max score 97.24.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 26.4122 / max 400.1488, expressed in 1807 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
54222	22.9267	1804
54221	3.4176	1344
54223	0.0679	22

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	97.24	gold quality
calcaneal tendon	UBERON:0003701	93.02	gold quality
secondary oocyte	CL:0000655	92.56	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	91.88	gold quality
adrenal tissue	UBERON:0018303	88.97	gold quality
ventricular zone	UBERON:0003053	88.49	gold quality
ganglionic eminence	UBERON:0004023	88.28	gold quality
popliteal artery	UBERON:0002250	87.49	gold quality
tibial artery	UBERON:0007610	87.49	gold quality
right testis	UBERON:0004534	87.29	gold quality
gastrocnemius	UBERON:0001388	87.26	gold quality
left testis	UBERON:0004533	87.26	gold quality
hindlimb stylopod muscle	UBERON:0004252	87.25	gold quality
muscle of leg	UBERON:0001383	86.90	gold quality
aorta	UBERON:0000947	86.83	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	86.64	gold quality
testis	UBERON:0000473	86.58	gold quality
islet of Langerhans	UBERON:0000006	86.53	gold quality
left coronary artery	UBERON:0001626	86.43	gold quality
monocyte	CL:0000576	86.10	gold quality
thoracic aorta	UBERON:0001515	86.10	gold quality
ascending aorta	UBERON:0001496	86.09	gold quality
descending thoracic aorta	UBERON:0002345	86.00	gold quality
omental fat pad	UBERON:0010414	85.75	gold quality
rectum	UBERON:0001052	85.74	gold quality
peritoneum	UBERON:0002358	85.72	gold quality
mononuclear cell	CL:0000842	85.66	gold quality
adipose tissue of abdominal region	UBERON:0007808	85.53	gold quality
tibial nerve	UBERON:0001323	85.50	gold quality
leukocyte	CL:0000738	85.49	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.55

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AR

miRNA regulators (miRDB)

47 targeting ANAPC10, 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-5011-5P	100.00	83.46	5820
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-190A-3P	100.00	80.35	5520
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-186-5P	99.99	70.83	3707
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-MIR-4495	99.82	72.08	3080
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-548M	99.70	68.87	1749
HSA-MIR-7156-5P	99.64	68.81	1369
HSA-MIR-651-5P	99.64	68.49	1104
HSA-MIR-5584-5P	99.49	68.22	2814
HSA-MIR-1324	99.46	66.57	1302
HSA-MIR-4273	99.45	67.93	1206
HSA-MIR-4666A-5P	99.41	69.72	1887

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 98.2% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 3)

• Substrates are recruited to the Anaphase-promoting complex by binding to a bipartite substrate receptor composed of Cdh1 and Doc1. (PMID:21186364)
• Cdc20 requires APC3 and APC8 to bind and activate the APC/C when the spindle assembly checkpoint is satisfied, but only APC8 when active, and APC10 is crucial for the destruction of cyclin B1 and securin, but not cyclin A (PMID:21336306)
• APC10 was overexpressed in non-small cell lung cancer cell lines compared to human bronchial epithelial cell lines. APC10 was shown to interact with GAC; knocking down APC10 downregulated glutamine metabolism to induce autophagy, resulting in effective inhibition of the proliferation and migration of non-small cell lung cancer cells. (PMID:31023143)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	anapc10	ENSDARG00000090152
mus_musculus	Anapc10	ENSMUSG00000036977
rattus_norvegicus	Anapc10	ENSRNOG00000018296
drosophila_melanogaster	APC10	FBGN0034231
caenorhabditis_elegans		WBGENE00000144
caenorhabditis_elegans	Y48G1C.12	WBGENE00044345

Protein

Protein identifiers

Anaphase-promoting complex subunit 10 — Q9UM13 (reviewed: Q9UM13)

Alternative names: Cyclosome subunit 10

All UniProt accessions (6): A0A286YEY6, D6R9Q5, D6RA92, D6RB36, D6RD74, Q9UM13

UniProt curated annotations — full annotation on UniProt →

Function. Component of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin ligase that controls progression through mitosis and the G1 phase of the cell cycle. The APC/C complex acts by mediating ubiquitination and subsequent degradation of target proteins: it mainly mediates the formation of ‘Lys-11’-linked polyubiquitin chains and, to a lower extent, the formation of ‘Lys-48’- and ‘Lys-63’-linked polyubiquitin chains. The APC/C complex catalyzes assembly of branched ‘Lys-11’-/‘Lys-48’-linked branched ubiquitin chains on target proteins.

Subunit / interactions. The mammalian APC/C is composed at least of 14 distinct subunits ANAPC1, ANAPC2, CDC27/APC3, ANAPC4, ANAPC5, CDC16/APC6, ANAPC7, CDC23/APC8, ANAPC10, ANAPC11, CDC26/APC12, ANAPC13, ANAPC15 and ANAPC16 that assemble into a complex of at least 19 chains with a combined molecular mass of around 1.2 MDa; APC/C interacts with FZR1 and FBXO5. The C-terminus of APC10 binds to CDC27/APC3. Interacts with PIWIL1; interaction only takes place when PIWIL1 binds piRNA. Interacts with FBXO43; the interaction is direct.

Pathway. Protein modification; protein ubiquitination.

Similarity. Belongs to the APC10 family.

RefSeq proteins (9): NP_001243635, NP_001243636, NP_001243637, NP_001243638, NP_001243639, NP_001243640, NP_001243641, NP_001305296, NP_055700 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004939	APC_su10/DOC_dom	Domain
IPR008979	Galactose-bd-like_sf	Homologous_superfamily
IPR016901	APC10/Doc1	Family

Pfam: PF03256

UniProt features (29 total): strand 12, helix 8, sequence conflict 3, modified residue 2, initiator methionine 1, chain 1, domain 1, sequence variant 1

Structure

Experimental structures (PDB)

21 structures.

PDB	Method	Resolution (Å)
1JHJ	X-RAY DIFFRACTION	1.6
9GAW	ELECTRON MICROSCOPY	2.9
6Q6G	ELECTRON MICROSCOPY	3.2
6Q6H	ELECTRON MICROSCOPY	3.2
8PKP	ELECTRON MICROSCOPY	3.2
5G05	ELECTRON MICROSCOPY	3.4
8TAU	ELECTRON MICROSCOPY	3.5
4UI9	ELECTRON MICROSCOPY	3.6
6TNT	ELECTRON MICROSCOPY	3.78
6TLJ	ELECTRON MICROSCOPY	3.8
5G04	ELECTRON MICROSCOPY	3.9
6TM5	ELECTRON MICROSCOPY	3.9
9N9R	ELECTRON MICROSCOPY	3.9
9N9S	ELECTRON MICROSCOPY	3.9
8TAR	ELECTRON MICROSCOPY	4
5LCW	ELECTRON MICROSCOPY	4.2
5A31	ELECTRON MICROSCOPY	4.3
5KHU	ELECTRON MICROSCOPY	4.8
5KHR	ELECTRON MICROSCOPY	6.1
5L9T	ELECTRON MICROSCOPY	6.4
5L9U	ELECTRON MICROSCOPY	6.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UM13-F1	90.31	0.76

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 (2): 2, 169

Function

Pathways and Gene Ontology

Reactome pathways

47 pathways

ID	Pathway
R-HSA-141430	Inactivation of APC/C via direct inhibition of the APC/C complex
R-HSA-174048	APC/C:Cdc20 mediated degradation of Cyclin B
R-HSA-174084	Autodegradation of Cdh1 by Cdh1:APC/C
R-HSA-174154	APC/C:Cdc20 mediated degradation of Securin
R-HSA-174178	APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1
R-HSA-174184	Cdc20:Phospho-APC/C mediated degradation of Cyclin A
R-HSA-176407	Conversion from APC/C:Cdc20 to APC/C:Cdh1 in late anaphase
R-HSA-176408	Regulation of APC/C activators between G1/S and early anaphase
R-HSA-176409	APC/C:Cdc20 mediated degradation of mitotic proteins
R-HSA-176412	Phosphorylation of the APC/C
R-HSA-179409	APC-Cdc20 mediated degradation of Nek2A
R-HSA-2467813	Separation of Sister Chromatids
R-HSA-2559582	Senescence-Associated Secretory Phenotype (SASP)
R-HSA-68867	Assembly of the pre-replicative complex
R-HSA-69017	CDK-mediated phosphorylation and removal of Cdc6
R-HSA-8853884	Transcriptional Regulation by VENTX
R-HSA-9687136	Aberrant regulation of mitotic exit in cancer due to RB1 defects
R-HSA-983168	Antigen processing: Ubiquitination & Proteasome degradation
R-HSA-1280218	Adaptive Immune System
R-HSA-141405	Inhibition of the proteolytic activity of APC/C required for the onset of anaphase by mitotic spindle checkpoint components
R-HSA-1640170	Cell Cycle
R-HSA-1643685	Disease
R-HSA-168256	Immune System
R-HSA-174143	APC/C-mediated degradation of cell cycle proteins
R-HSA-176814	Activation of APC/C and APC/C:Cdc20 mediated degradation of mitotic proteins
R-HSA-179419	APC:Cdc20 mediated degradation of cell cycle proteins prior to satisfation of the cell cycle checkpoint
R-HSA-212436	Generic Transcription Pathway
R-HSA-2262752	Cellular responses to stress
R-HSA-2555396	Mitotic Metaphase and Anaphase
R-HSA-2559583	Cellular Senescence

MSigDB gene sets: 193 (showing top): ATF_B, REACTOME_DNA_REPLICATION, REACTOME_APC_C_CDH1_MEDIATED_DEGRADATION_OF_CDC20_AND_OTHER_APC_C_CDH1_TARGETED_PROTEINS_IN_LATE_MITOSIS_EARLY_G1, REACTOME_APC_C_CDC20_MEDIATED_DEGRADATION_OF_CYCLIN_B, REACTOME_CONVERSION_FROM_APC_C_CDC20_TO_APC_C_CDH1_IN_LATE_ANAPHASE, REACTOME_PHOSPHORYLATION_OF_THE_APC_C, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, REACTOME_ANTIGEN_PROCESSING_UBIQUITINATION_PROTEASOME_DEGRADATION, GOBP_ANAPHASE_PROMOTING_COMPLEX_DEPENDENT_CATABOLIC_PROCESS, REACTOME_APC_CDC20_MEDIATED_DEGRADATION_OF_NEK2A, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_REGULATION_OF_MEIOTIC_CELL_CYCLE, CAGCTG_AP4_Q5, PUJANA_CHEK2_PCC_NETWORK

GO Biological Process (8): regulation of mitotic cell cycle (GO:0007346), anaphase-promoting complex-dependent catabolic process (GO:0031145), cell division (GO:0051301), regulation of meiotic cell cycle (GO:0051445), protein K48-linked ubiquitination (GO:0070936), protein K11-linked ubiquitination (GO:0070979), protein branched polyubiquitination (GO:0141198), protein ubiquitination (GO:0016567)

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

GO Cellular Component (4): nucleoplasm (GO:0005654), anaphase-promoting complex (GO:0005680), cytosol (GO:0005829), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-15 pathways:

Category	Pathways
APC/C-mediated degradation of cell cycle proteins	4
APC/C:Cdc20 mediated degradation of mitotic proteins	2
APC:Cdc20 mediated degradation of cell cycle proteins prior to satisfation of the cell cycle checkpoint	2
Activation of APC/C and APC/C:Cdc20 mediated degradation of mitotic proteins	2
Inhibition of the proteolytic activity of APC/C required for the onset of anaphase by mitotic spindle checkpoint components	1
Mitotic Anaphase	1
Cellular Senescence	1
DNA Replication Pre-Initiation	1
Switching of origins to a post-replicative state	1
Generic Transcription Pathway	1
Aberrant regulation of mitotic cell cycle due to RB1 defects	1
Class I MHC mediated antigen processing & presentation	1
Immune System	1
Regulation of APC/C activators between G1/S and early anaphase	1
Mitotic Spindle Checkpoint	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein polyubiquitination	3
cellular anatomical structure	3
regulation of cell cycle	2
mitotic cell cycle	1
proteasome-mediated ubiquitin-dependent protein catabolic process	1
cellular process	1
meiotic cell cycle	1
regulation of reproductive process	1
protein modification by small protein conjugation	1
binding	1
nuclear lumen	1
nuclear ubiquitin ligase complex	1
cullin-RING ubiquitin ligase complex	1
cytoplasm	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

2042 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ANAPC10	ANAPC11	Q9NYG5	998
ANAPC10	CDC23	Q9UJX2	993
ANAPC10	CDC16	Q13042	983
ANAPC10	CDC27	P30260	982
ANAPC10	ANAPC5	Q9UJX4	977
ANAPC10	CDC20	Q12834	968
ANAPC10	ANAPC13	Q9BS18	963
ANAPC10	CDC26	Q8NHZ8	959
ANAPC10	ANAPC7	Q9UJX3	952
ANAPC10	CUL9	Q8IWT3	865
ANAPC10	ANAPC16	Q96DE5	865
ANAPC10	ANAPC15	P60006	856
ANAPC10	ANAPC1	Q9H1A4	852
ANAPC10	ANAPC2	Q9UJX6	808
ANAPC10	UBE2S	Q16763	805

IntAct

86 interactions, top by confidence:

A	B	Type	Score
CDC20	BUB1B	psi-mi:“MI:0914”(association)	0.980
ANAPC2	CDC27	psi-mi:“MI:0915”(physical association)	0.910
PPP2R1A	STRN	psi-mi:“MI:0914”(association)	0.880
CDC27	ANAPC4	psi-mi:“MI:0914”(association)	0.860
ANAPC4	CDC27	psi-mi:“MI:0914”(association)	0.860
ANAPC5	CDC27	psi-mi:“MI:0914”(association)	0.810
CDC16	BUB1B	psi-mi:“MI:0914”(association)	0.790
CDC23	BUB1B	psi-mi:“MI:0914”(association)	0.790
ANAPC16	BUB1B	psi-mi:“MI:0914”(association)	0.730
ANAPC2	BUB1B	psi-mi:“MI:0914”(association)	0.730
CDC20	BUB1	psi-mi:“MI:0914”(association)	0.730
ANAPC10	CDC16	psi-mi:“MI:0915”(physical association)	0.710
ANAPC13	CDC27	psi-mi:“MI:0914”(association)	0.640
CDC26	BUB1B	psi-mi:“MI:0914”(association)	0.640
C16orf87	CDC27	psi-mi:“MI:0914”(association)	0.640
CDC27	NEK2	psi-mi:“MI:0914”(association)	0.620
SMPD2	MTHFR	psi-mi:“MI:0914”(association)	0.560

BioGRID (154): ANAPC10 (Affinity Capture-MS), ANAPC10 (Affinity Capture-Western), ANAPC10 (Affinity Capture-MS), ANAPC10 (Protein-peptide), ANAPC10 (Affinity Capture-MS), ANAPC10 (Affinity Capture-MS), ANAPC10 (Affinity Capture-MS), ANAPC10 (Co-purification), ANAPC10 (Affinity Capture-Western), ANAPC10 (Co-fractionation), ANAPC10 (Co-fractionation), ANAPC10 (Co-fractionation), ANAPC10 (Co-fractionation), ANAPC10 (Co-fractionation), ANAPC2 (Co-fractionation)

ESM2 similar proteins: A0A2R8RWN9, A0JN27, A1L3K1, B5DFI8, B5DFK7, F1LTR1, G3MWR8, P06730, P17870, P20461, P29066, P29338, P32120, P32121, P49407, P51466, P51467, P63073, P63074, Q13888, Q16763, Q1RML1, Q28D01, Q2HJ19, Q2TBV5, Q2YDH1, Q4R562, Q4W5Z4, Q5JUK3, Q5RCR4, Q5SP67, Q5SRY7, Q5ZJX1, Q6P1K8, Q7RTP6, Q8BWG8, Q8C6G8, Q8CJ19, Q8K2H6, Q8VCV1

Diamond homologs: H2L2B8, O42971, P53068, Q2YDH1, Q55ER5, Q8K2H6, Q9UM13, Q9V831, Q9ZPW2, Q5SSH7, D3ZEF4, O43149, O95714, Q14999, Q3U487, Q4U2R1, Q5RCJ3, Q5T447, Q80TT8, Q8IWT3, Q8VE73

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
ANAPC10	“form complex”	APC-c	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 61 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
Inhibition of the proteolytic activity of APC/C required for the onset of anaphase by mitotic spindle checkpoint components	13	206.2×	5e-27
Inactivation of APC/C via direct inhibition of the APC/C complex	13	168.7×	5e-26
APC-Cdc20 mediated degradation of Nek2A	14	148.0×	9e-27
APC:Cdc20 mediated degradation of cell cycle proteins prior to satisfation of the cell cycle checkpoint	14	148.0×	9e-27
Activation of APC/C and APC/C:Cdc20 mediated degradation of mitotic proteins	14	142.8×	1e-26
Conversion from APC/C:Cdc20 to APC/C:Cdh1 in late anaphase	11	142.8×	6e-21
Phosphorylation of the APC/C	10	135.9×	6e-19
Aberrant regulation of mitotic exit in cancer due to RB1 defects	10	129.8×	1e-18

GO biological processes:

GO term	Partners	Fold	FDR
protein branched polyubiquitination	11	201.5×	4e-22
regulation of meiotic cell cycle	12	199.8×	8e-24
anaphase-promoting complex-dependent catabolic process	12	183.2×	2e-23
protein K11-linked ubiquitination	11	93.7×	7e-18
regulation of mitotic cell cycle	13	68.0×	3e-19
mitotic spindle assembly checkpoint signaling	5	61.1×	7e-07
protein K48-linked ubiquitination	11	40.3×	1e-13
cell division	18	18.1×	7e-17

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	24
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1340989	GRCh37/hg19 4q28.3-31.21(chr4:138289049-145923298)x1	Pathogenic

SpliceAI

1975 predictions. Top by Δscore:

Variant	Effect	Δscore
4:144995602:TG:T	acceptor_gain	1.0000
4:144995604:C:CC	acceptor_gain	1.0000
4:144995608:C:CT	acceptor_gain	1.0000
4:144995609:A:T	acceptor_gain	1.0000
4:145053644:AATT:A	donor_gain	1.0000
4:145081655:ATTAC:A	donor_loss	1.0000
4:145081656:TTA:T	donor_loss	1.0000
4:145081657:TA:T	donor_loss	1.0000
4:145081659:CC:C	donor_loss	1.0000
4:145096108:TATT:T	acceptor_gain	1.0000
4:145096114:A:C	acceptor_gain	1.0000
4:144995599:AGTTG:A	acceptor_gain	0.9900
4:144995600:GTTG:G	acceptor_gain	0.9900
4:144995601:TTG:T	acceptor_gain	0.9900
4:144995602:TGC:T	acceptor_loss	0.9900
4:144995604:C:CG	acceptor_loss	0.9900
4:144995605:T:G	acceptor_loss	0.9900
4:145059957:C:CT	donor_gain	0.9900
4:145059958:T:TT	donor_gain	0.9900
4:145064690:CTT:C	acceptor_gain	0.9900
4:145064691:TT:T	acceptor_gain	0.9900
4:145064693:C:CC	acceptor_gain	0.9900
4:145064700:CAA:C	acceptor_gain	0.9900
4:145064701:A:T	acceptor_gain	0.9900
4:145081751:C:CC	acceptor_gain	0.9900
4:145081751:CTA:C	acceptor_loss	0.9900
4:145081752:T:A	acceptor_loss	0.9900
4:145096110:TT:T	acceptor_gain	0.9900
4:145096112:C:CC	acceptor_gain	0.9900
4:145098118:A:AC	donor_gain	0.9900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000003245 (4:145016836 T>TAAA), RS1000009618 (4:145019956 CAA>C,CA,CAAA), RS1000062759 (4:145022206 C>A), RS1000070659 (4:145066262 G>T), RS1000092242 (4:145099584 GGA>G), RS1000094296 (4:145061618 A>G), RS1000114665 (4:145022546 A>T), RS1000123345 (4:145099878 C>T), RS1000127929 (4:145073331 T>C), RS1000158993 (4:145073073 T>C), RS10001640 (4:145037047 T>C), RS1000164923 (4:145018098 C>A,G,T), RS1000189363 (4:145068147 A>C), RS1000231196 (4:145022809 A>G), RS1000270711 (4:145064582 T>C)

Disease associations

OMIM: gene MIM:613745 | disease phenotypes: MIM:277000

GenCC curated gene-disease

Mondo (1): Mayer-Rokitansky-Kuster-Hauser syndrome type 1 (MONDO:0010173)

Orphanet (1): Mayer-Rokitansky-Küster-Hauser syndrome type 1 (Orphanet:247775)

HPO phenotypes

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

GWAS associations

49 associations (top):

Study	Trait	p-value
GCST002115_7	Axial length	5.000000e-11
GCST002647_143	Height	3.000000e-43
GCST002702_43	Height	2.000000e-12
GCST004029_18	Angiotensin-converting enzyme inhibitor intolerance	9.000000e-06
GCST004029_23	Angiotensin-converting enzyme inhibitor intolerance	4.000000e-06
GCST004066_30	Hip circumference	7.000000e-16
GCST004066_81	Hip circumference	4.000000e-15
GCST004602_31	Mean corpuscular volume	7.000000e-12
GCST004605_70	Mean corpuscular hemoglobin concentration	3.000000e-10
GCST004609_53	Monocyte percentage of white cells	1.000000e-09
GCST004625_11	Monocyte count	3.000000e-10
GCST005956_60	Waist-to-hip ratio adjusted for BMI	2.000000e-08
GCST005962_45	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	2.000000e-06
GCST007611_17	Chronic obstructive pulmonary disease or high blood pressure (pleiotropy)	1.000000e-18
GCST007656_19	Chronic obstructive pulmonary disease or resting heart rate (pleiotropy)	2.000000e-19
GCST008839_260	Height	9.000000e-14
GCST010701_94	Cortical surface area (MOSTest)	2.000000e-13
GCST010702_38	Subcortical volume (MOSTest)	1.000000e-10
GCST010703_203	Brain morphology (MOSTest)	1.000000e-11
GCST010725_4	Malaria	4.000000e-10
GCST010725_84	Malaria	7.000000e-11
GCST010725_89	Malaria	7.000000e-11
GCST010988_83	Adult body size	8.000000e-09
GCST012227_1316	Hip circumference adjusted for BMI	4.000000e-31
GCST012227_1317	Hip circumference adjusted for BMI	5.000000e-10
GCST012227_1320	Hip circumference adjusted for BMI	2.000000e-13
GCST012227_1324	Hip circumference adjusted for BMI	2.000000e-09
GCST012227_1325	Hip circumference adjusted for BMI	2.000000e-18
GCST012228_76	Waist-hip index	2.000000e-09
GCST012230_275	Waist-to-hip ratio adjusted for BMI	2.000000e-10

EFO canonical traits (14, from GWAS)

EFO ID	Trait name
EFO:0005318	axial length measurement
EFO:0005325	response to angiotensin-converting enzyme inhibitor
EFO:0004528	mean corpuscular hemoglobin concentration
EFO:0007989	monocyte percentage of leukocytes
EFO:0005091	monocyte count
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement
EFO:0004346	neuroimaging measurement
EFO:0008039	BMI-adjusted hip circumference
EFO:0004980	appendicular lean mass
EFO:0007986	reticulocyte count
EFO:0010701	mean reticulocyte volume
EFO:0007789	BMI-adjusted waist circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
methylmercuric chloride	decreases expression	2
Air Pollutants	decreases expression, increases abundance, increases expression	2
Tretinoin	decreases expression	2
Valproic Acid	affects expression, decreases expression	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
aristolochic acid I	decreases expression	1
dicrotophos	decreases expression	1
pirinixic acid	affects binding, increases activity, increases expression	1
bisphenol A	affects cotreatment, increases expression	1
beta-lapachone	decreases expression, increases expression	1
manganese chloride	increases abundance, increases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
beta-methylcholine	affects expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
abrine	increases expression	1
Rosiglitazone	decreases expression	1
Sunitinib	decreases expression	1
Leflunomide	increases expression	1
Acetaminophen	decreases expression	1
Chelating Agents	affects binding, increases expression	1
Copper	affects binding, increases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Indomethacin	affects cotreatment, increases expression	1
Manganese	increases abundance, increases expression	1
Methyl Methanesulfonate	increases expression	1
Phenobarbital	affects expression	1
Quercetin	decreases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1
Cyclosporine	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01911884	Not specified	COMPLETED	Assessment of Quality of Global and Sexual Life and Impact of Surgical and Non Surgical Vaginal Aplasia in Patients With a Rokitansky Syndrome
NCT05415540	Not specified	COMPLETED	Evolution of the Quality of Life and Experience of Young Women With Utero-vaginal Aplasia (MRKHPSY)
NCT07186764	Not specified	RECRUITING	Evaluation of the Quality of Life and Gynecological Follow-up of Patients Treated for Mayer-Rokitansky-Küster-Hauser (MRKH) Syndrome
NCT07321782	Not specified	NOT_YET_RECRUITING	Clinical and Imaging Features in MRKH Syndrome