TRIM36

Summary

TRIM36 (tripartite motif containing 36, HGNC:16280) is a protein-coding gene on chromosome 5q22.3, encoding E3 ubiquitin-protein ligase TRIM36 (Q9NQ86). E3 ubiquitin-protein ligase which mediates ubiquitination and subsequent proteasomal degradation of target proteins.

The protein encoded by this gene is a member of the tripartite motif (TRIM) family. The TRIM motif includes three zinc-binding domains, a RING, a B-box type 1 and a B-box type 2, and a coiled-coil region. Multiple alternatively spliced transcript variants that encode different protein isoforms have been described for this gene.

Source: NCBI Gene 55521 — RefSeq curated summary.

At a glance

• Gene–disease (curated): anencephaly 1 (Limited, GenCC)
• GWAS associations: 21
• Clinical variants (ClinVar): 124 total — 1 pathogenic
• Phenotypes (HPO): 4
• MANE Select transcript: NM_001300759

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16280
Approved symbol	TRIM36
Name	tripartite motif containing 36
Location	5q22.3
Locus type	gene with protein product
Status	Approved
Aliases	RBCC728, RNF98, HAPRIN
Ensembl gene	ENSG00000152503
Ensembl biotype	protein_coding
OMIM	609317
Entrez	55521

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 7 protein_coding, 4 protein_coding_CDS_not_defined

ENST00000282369, ENST00000379617, ENST00000379618, ENST00000508894, ENST00000510222, ENST00000511701, ENST00000513154, ENST00000513485, ENST00000514154, ENST00000515104, ENST00000923549

RefSeq mRNA: 5 — MANE Select: NM_001300759 NM_001017397, NM_001017398, NM_001300752, NM_001300759, NM_018700

CCDS: CCDS34211, CCDS34212, CCDS4115, CCDS75287, CCDS78047

Canonical transcript exons

ENST00000513154 — 10 exons

Exon	Start	End
ENSE00001005556	115141279	115141374
ENSE00001005557	115133860	115134147
ENSE00001005560	115130592	115130889
ENSE00001005562	115137363	115137616
ENSE00001005567	115137000	115137124
ENSE00002021562	115124772	115126857
ENSE00002086279	115169608	115169908
ENSE00003470876	115163518	115163752
ENSE00003626843	115147069	115147394
ENSE00003649443	115144598	115144744

Expression profiles

Bgee: expression breadth ubiquitous, 223 present calls, max score 99.24.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.2137 / max 405.9765, expressed in 1106 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
62990	5.8204	1007
62993	1.0863	290
62989	0.5930	312
62991	0.4868	223
62994	0.1120	49
62995	0.1092	46
62992	0.0060	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	99.24	gold quality
secondary oocyte	CL:0000655	98.89	gold quality
left testis	UBERON:0004533	97.80	gold quality
right testis	UBERON:0004534	97.67	gold quality
cortical plate	UBERON:0005343	96.88	gold quality
oocyte	CL:0000023	95.49	gold quality
testis	UBERON:0000473	95.15	gold quality
male germ cell	CL:0000015	94.94	gold quality
jejunal mucosa	UBERON:0000399	93.22	gold quality
ganglionic eminence	UBERON:0004023	92.70	gold quality
pons	UBERON:0000988	92.39	gold quality
dorsal root ganglion	UBERON:0000044	90.91	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	89.57	gold quality
pigmented layer of retina	UBERON:0001782	89.14	gold quality
retina	UBERON:0000966	89.12	gold quality
CA1 field of hippocampus	UBERON:0003881	88.44	gold quality
ventricular zone	UBERON:0003053	87.93	gold quality
prefrontal cortex	UBERON:0000451	87.56	gold quality
Brodmann (1909) area 23	UBERON:0013554	87.49	gold quality
superior vestibular nucleus	UBERON:0007227	87.09	gold quality
substantia nigra pars compacta	UBERON:0001965	86.71	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.57	gold quality
superior frontal gyrus	UBERON:0002661	86.56	gold quality
orbitofrontal cortex	UBERON:0004167	86.33	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	86.15	gold quality
spinal cord	UBERON:0002240	85.74	gold quality
colonic mucosa	UBERON:0000317	85.55	gold quality
duodenum	UBERON:0002114	85.52	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	85.44	gold quality
mucosa of sigmoid colon	UBERON:0004993	85.40	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-GEOD-134144	yes	32.56
E-ANND-3	no	5.52

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

161 targeting TRIM36, 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-3646	100.00	73.56	5283
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-146A-5P	99.96	68.93	988

Literature-anchored findings (GeneRIF, showing 13)

• The overexpression of the TRIM36 in the vast majority of prostate cancer suggest that this gene might be involved in the prostate tumorigenesis. (PMID:15145053)
• molecular cloning and characterization of a human haprin ortholog. (PMID:15955891)
• TRIM36 has a ubiquitin ligase activity and interacts with centromere protein-H, potentially associated with chromosome segregation and its excess may cause chromosomal instability. (PMID:19232519)
• TRIM36 is the causative gene for autosomal recessive anencephaly (PMID:28087737)
• The siRNA knock down of TRIM36 in HeLa and LN229 cells also led to reduced cell proliferation and increased apoptosis. We suggest that microtubule disruption and disorganized spindles mediated by mutant TRIM36 affect neural cell proliferation during neural tube formation, leading to Anencephaly . (PMID:28087737)
• aberrant hypermethylation of TRIM36 might be involved in the acquisition of malignant phenotype and could be served as a biomarker for risk assessment of PAHs exposure (PMID:28359976)
• TRIM36 is a novel androgen-responsive gene, and it dramatically enhanced the efficacy of anti-androgen drugs against prostate cancer. (PMID:29449534)
• Results suggest that high expression of TRIM36 is associated with favorable prognosis and that TRIM36 plays a tumor-suppressive role by inhibiting cell proliferation and migration as well as promoting apoptosis in prostate cancer. (PMID:30238687)
• TRIM36 suppresses cell growth and promotes apoptosis in human esophageal squamous cell carcinoma cells by inhibiting Wnt/beta-catenin signaling pathway. (PMID:35768649)
• TRIM36 enhances lung adenocarcinoma radiosensitivity and inhibits tumorigenesis through promoting RAD51 ubiquitination and antagonizing hsa-miR-376a-5p. (PMID:36058131)
• Trigred motif 36 regulates neuroendocrine differentiation of prostate cancer via HK2 ubiquitination and GPx4 deficiency. (PMID:36799474)
• Genome-wide association study reveals HSF2, GJA1 and TRIM36 as susceptibility genes for preeclampsia: a community-based population study in Tianjin, China. (PMID:37735976)
• FOXA2 Suppression by TRIM36 Exerts Anti-Tumor Role in Colorectal Cancer Via Inducing NRF2/GPX4-Regulated Ferroptosis. (PMID:37875418)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	trim36	ENSDARG00000062794
mus_musculus	Trim36	ENSMUSG00000033949
rattus_norvegicus	Trim36	ENSRNOG00000016612

Paralogs (80): MID2 (ENSG00000080561), TRIM9 (ENSG00000100505), MID1 (ENSG00000101871), MEFV (ENSG00000103313), TRIM35 (ENSG00000104228), TRIM14 (ENSG00000106785), TRIM37 (ENSG00000108395), TRIM2 (ENSG00000109654), TRIM3 (ENSG00000110171), TRIM38 (ENSG00000112343), TRIM62 (ENSG00000116525), TRIM67 (ENSG00000119283), TRIM32 (ENSG00000119401), BSPRY (ENSG00000119411), TRIM25 (ENSG00000121060), TRIM6 (ENSG00000121236), TRIM24 (ENSG00000122779), TRIM51 (ENSG00000124900), TRIM28 (ENSG00000130726), TRIM21 (ENSG00000132109), TRIM5 (ENSG00000132256), TRIM22 (ENSG00000132274), TRIM47 (ENSG00000132481), TRIM45 (ENSG00000134253), TRIM29 (ENSG00000137699), TRIM54 (ENSG00000138100), PML (ENSG00000140464), TRIM65 (ENSG00000141569), TRIM43B (ENSG00000144010), TRIM43 (ENSG00000144015), TRIM7 (ENSG00000146054), TRIM41 (ENSG00000146063), TRIM50 (ENSG00000146755), TRIM4 (ENSG00000146833), TRIM55 (ENSG00000147573), TRIM48 (ENSG00000150244), TRIM11 (ENSG00000154370), TRIM74 (ENSG00000155428), TRIM42 (ENSG00000155890), TRIM63 (ENSG00000158022)

Protein

Protein identifiers

E3 ubiquitin-protein ligase TRIM36 — Q9NQ86 (reviewed: Q9NQ86)

Alternative names: RING finger protein 98, RING-type E3 ubiquitin transferase TRIM36, Tripartite motif-containing protein 36, Zinc-binding protein Rbcc728

All UniProt accessions (3): Q9NQ86, D6RAU9, E9PBG3

UniProt curated annotations — full annotation on UniProt →

Function. E3 ubiquitin-protein ligase which mediates ubiquitination and subsequent proteasomal degradation of target proteins. Involved in chromosome segregation and cell cycle regulation. May play a role in the acrosome reaction and fertilization.

Subunit / interactions. Interacts with CENPH.

Subcellular location. Cytoplasm. Cytoplasmic vesicle. Secretory vesicle. Acrosome. Cytoskeleton.

Tissue specificity. Highly expressed in testis, prostate and brain. Weakly expressed in kidney, lung and heart. Expressed in fetal tissues.

Disease relevance. Anencephaly 1 (ANPH1) [MIM:206500] An extreme form of neural tube defect resulting in the absence of brain tissues, and death in utero or perinatally. Infants are born with intact spinal cords, cerebellums, and brainstems, but lack formation of neural structures above this level. The skull is only partially formed. ANPH1 inheritance is autosomal recessive. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the TRIM/RBCC family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q9NQ86-1	1	yes
Q9NQ86-2	2
Q9NQ86-3	3
Q9NQ86-4	4

RefSeq proteins (5): NP_001017397, NP_001017398, NP_001287681, NP_001287688, NP_061170 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000315	Znf_B-box	Domain
IPR001841	Znf_RING	Domain
IPR001870	B30.2/SPRY	Domain
IPR003879	Butyrophylin_SPRY	Domain
IPR003961	FN3_dom	Domain
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR013320	ConA-like_dom_sf	Homologous_superfamily
IPR013783	Ig-like_fold	Homologous_superfamily
IPR017903	COS_domain	Domain
IPR017907	Znf_RING_CS	Conserved_site
IPR027370	Znf-RING_euk	Domain
IPR027726	Trim36_HC-RING	Domain
IPR035727	SPRY/PRY_TRIM36	Domain
IPR036116	FN3_sf	Homologous_superfamily
IPR040859	Midline-1_COS	Domain
IPR043136	B30.2/SPRY_sf	Homologous_superfamily
IPR047065	TRIM36_Bbox2_Zfn	Domain
IPR047066	TRIM36_Bbox1_Zfn	Domain
IPR050617	E3_ligase_FN3/SPRY	Family

Pfam: PF00041, PF00643, PF13445, PF18568, PF22586

UniProt features (45 total): strand 14, splice variant 5, sequence variant 5, helix 5, binding site 4, domain 3, turn 3, zinc finger region 3, chain 1, sequence conflict 1, coiled-coil region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
7QS4	X-RAY DIFFRACTION	2.25

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NQ86-F1	79.24	0.34

Functional residue map

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

Ligand- & substrate-binding residues (4): 235; 241; 212; 215

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-983168	Antigen processing: Ubiquitination & Proteasome degradation

MSigDB gene sets: 228 (showing top): GOBP_MITOTIC_CYTOKINESIS, GOBP_SINGLE_FERTILIZATION, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, BENPORATH_ES_WITH_H3K27ME3, FARMER_BREAST_CANCER_CLUSTER_7, GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, REACTOME_ANTIGEN_PROCESSING_UBIQUITINATION_PROTEASOME_DEGRADATION, GOCC_SECRETORY_GRANULE, BONCI_TARGETS_OF_MIR15A_AND_MIR16_1, GOBP_CYTOKINESIS, GOBP_REGULATION_OF_CELL_CYCLE, ATTACAT_MIR3803P, GOBP_MITOTIC_CELL_CYCLE

GO Biological Process (5): mitotic cytokinesis (GO:0000281), spindle organization (GO:0007051), acrosome reaction (GO:0007340), regulation of cell cycle (GO:0051726), regulation of microtubule cytoskeleton organization (GO:0070507)

GO Molecular Function (7): ubiquitin-protein transferase activity (GO:0004842), zinc ion binding (GO:0008270), alpha-tubulin binding (GO:0043014), ubiquitin protein ligase activity (GO:0061630), protein binding (GO:0005515), transferase activity (GO:0016740), metal ion binding (GO:0046872)

GO Cellular Component (7): acrosomal vesicle (GO:0001669), cytoplasm (GO:0005737), cytosol (GO:0005829), cytoskeleton (GO:0005856), plasma membrane (GO:0005886), transport vesicle (GO:0030133), cytoplasmic vesicle (GO:0031410)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Class I MHC mediated antigen processing & presentation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
microtubule cytoskeleton organization	2
cellular anatomical structure	2
cytoplasm	2
mitotic cell cycle	1
cytoskeleton-dependent cytokinesis	1
mitotic cell cycle process	1
cell cycle process	1
membrane fusion involved in acrosome reaction	1
single fertilization	1
reproductive process	1
acrosomal vesicle exocytosis	1
cell cycle	1
regulation of cellular process	1
regulation of microtubule-based process	1
regulation of cytoskeleton organization	1
ubiquitin-like protein transferase activity	1
transition metal ion binding	1
tubulin binding	1
ubiquitin-protein transferase activity	1
ubiquitin-like protein ligase activity	1
binding	1
catalytic activity	1
cation binding	1
secretory granule	1
intracellular anatomical structure	1
intracellular membraneless organelle	1
membrane	1
cell periphery	1
endomembrane system	1
cytoplasmic vesicle	1
intracellular vesicle	1

Protein interactions and networks

STRING

1053 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TRIM36	CENPH	Q9H3R5	850
TRIM36	TMLHE	Q9NVH6	831
TRIM36	TRAT1	Q6PIZ9	820
TRIM36	BBOX1	O75936	718
TRIM36	SPRY1	O43609	649
TRIM36	WFDC3	Q8IUB2	511
TRIM36	TRIM41	Q8WV44	503
TRIM36	SH3RF1	Q7Z6J0	471
TRIM36	HERC2	O95714	462
TRIM36	AREL1	O15033	462
TRIM36	NEDD4L	Q96PU5	454
TRIM36	TRIM75	A6NK02	435
TRIM36	NCBP2	P52298	430
TRIM36	H0Y8G9	H0Y8G9	427
TRIM36	HERC3	Q15034	426

IntAct

41 interactions, top by confidence:

A	B	Type	Score
TRIM36	GLRX3	psi-mi:“MI:0915”(physical association)	0.720
GLRX3	TRIM36	psi-mi:“MI:0915”(physical association)	0.720
EIF4A2	TRIM36	psi-mi:“MI:0915”(physical association)	0.560
TRIM36	EIF4A2	psi-mi:“MI:0915”(physical association)	0.560
TRIM36	GRB7	psi-mi:“MI:0915”(physical association)	0.560
ZNF417	TRIM36	psi-mi:“MI:0915”(physical association)	0.560
TRIM36	ZMAT2	psi-mi:“MI:0915”(physical association)	0.560
ZNF587	TRIM36	psi-mi:“MI:0915”(physical association)	0.560
TRIM36	TRAF3IP3	psi-mi:“MI:0915”(physical association)	0.560
TRIM36	ZNF417	psi-mi:“MI:0915”(physical association)	0.560
ZMAT2	TRIM36	psi-mi:“MI:0915”(physical association)	0.560
GRB7	TRIM36	psi-mi:“MI:0915”(physical association)	0.560
TRIM36	BTRC	psi-mi:“MI:0915”(physical association)	0.560
KIAA0753	OFD1	psi-mi:“MI:2364”(proximity)	0.480
TRIM36	HSP90AB1	psi-mi:“MI:0915”(physical association)	0.400
TRIM36	TRIM36	psi-mi:“MI:0915”(physical association)	0.370
UBE2H	TRIM36	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (154): TRIM36 (Two-hybrid), TRIM36 (Two-hybrid), TRIM36 (Two-hybrid), TRIM36 (Two-hybrid), TRAF3IP3 (Two-hybrid), ZNF587 (Two-hybrid), ZNF417 (Two-hybrid), ZMAT2 (Two-hybrid), TRIM36 (Synthetic Lethality), TRIM36 (Proximity Label-MS), TRIM36 (Proximity Label-MS), TRIM36 (Proximity Label-MS), TRIM36 (Proximity Label-MS), TRIM36 (Proximity Label-MS), TRIM36 (Synthetic Lethality)

ESM2 similar proteins: A1L4K1, D4A7V9, E9QHE3, F1LW30, H0UZ81, O15344, O70583, O95361, P82457, P82458, P97573, Q14258, Q14596, Q28CB1, Q38HM4, Q3UMR0, Q3V3A7, Q58D15, Q5F479, Q5R760, Q5RC94, Q5REJ9, Q5REW9, Q5RF77, Q5XIH6, Q61510, Q6P549, Q6P6S3, Q6UXZ4, Q7T2L7, Q7TNH6, Q7Z494, Q80VK6, Q80WG7, Q8BZ52, Q8JZL1, Q8K1S2, Q8NFM7, Q91Z63, Q969Q1

Diamond homologs: A0A0G2JXN2, Q1XHU0, Q7TNM2, Q7Z4K8, Q80WG7, Q9HCM9, Q9NQ86, A0JN74, B0BLU1, B2RYR0, E7FAP1, F4I443, F6ZQ54, K7N6K2, O00635, O60858, O70418, P15533, P19474, P82457, Q0IIM1, Q0PF16, Q14258, Q1ACD5, Q1ACD6, Q1ACD7, Q1ACD8, Q28DL4, Q2YEM8, Q2YEM9, Q2YEN0, Q2YEN2, Q32L60, Q3TL54, Q3ZEE5, Q503I2, Q587N6, Q587N7, Q58DK8, Q5BN31

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
Ub:E2	“up-regulates activity”	TRIM36	ubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 22 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
Regulation of PLK1 Activity at G2/M Transition	5	37.3×	2e-05

GO biological processes:

GO term	Partners	Fold	FDR
cilium assembly	6	20.1×	6e-05
cell division	5	10.5×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	95
Likely benign	6
Benign	11

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
431166	NM_001300759.2(TRIM36):c.1486C>A (p.Pro496Thr)	Pathogenic

SpliceAI

2122 predictions. Top by Δscore:

Variant	Effect	Δscore
5:115130587:CCTA:C	donor_loss	1.0000
5:115130588:CTA:C	donor_loss	1.0000
5:115130590:A:T	donor_loss	1.0000
5:115133931:A:AC	donor_gain	1.0000
5:115133932:C:CC	donor_gain	1.0000
5:115133932:CT:C	donor_gain	1.0000
5:115133949:C:CT	donor_gain	1.0000
5:115133950:T:TT	donor_gain	1.0000
5:115133994:T:TA	donor_gain	1.0000
5:115134053:G:C	donor_gain	1.0000
5:115134145:TGC:T	acceptor_gain	1.0000
5:115134146:GCC:G	acceptor_loss	1.0000
5:115134148:C:CA	acceptor_loss	1.0000
5:115134148:C:CC	acceptor_gain	1.0000
5:115134157:T:C	acceptor_gain	1.0000
5:115134157:T:TC	acceptor_gain	1.0000
5:115134159:A:AC	acceptor_gain	1.0000
5:115134159:A:C	acceptor_gain	1.0000
5:115136993:GACTT:G	donor_loss	1.0000
5:115136994:ACTTA:A	donor_loss	1.0000
5:115136995:CT:C	donor_loss	1.0000
5:115136998:A:AC	donor_gain	1.0000
5:115136998:A:AG	donor_loss	1.0000
5:115136999:C:CA	donor_loss	1.0000
5:115136999:C:CC	donor_gain	1.0000
5:115136999:CCA:C	donor_gain	1.0000
5:115137123:TT:T	acceptor_gain	1.0000
5:115137125:C:CC	acceptor_gain	1.0000
5:115137126:T:C	acceptor_loss	1.0000
5:115137357:GAATA:G	donor_loss	1.0000

AlphaMissense

4778 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:115137382:C:G	A368P	1.000
5:115141346:A:G	L267P	1.000
5:115144646:A:C	H241Q	1.000
5:115144646:A:T	H241Q	1.000
5:115144664:A:C	C235W	1.000
5:115144665:C:G	C235S	1.000
5:115144665:C:T	C235Y	1.000
5:115144666:A:G	C235R	1.000
5:115144666:A:T	C235S	1.000
5:115144673:G:C	C232W	1.000
5:115144674:C:A	C232F	1.000
5:115144674:C:G	C232S	1.000
5:115144674:C:T	C232Y	1.000
5:115144675:A:G	C232R	1.000
5:115144675:A:T	C232S	1.000
5:115144677:A:T	V231D	1.000
5:115144690:A:G	C227R	1.000
5:115144697:A:C	C224W	1.000
5:115144698:C:A	C224F	1.000
5:115144698:C:G	C224S	1.000
5:115144698:C:T	C224Y	1.000
5:115144699:A:G	C224R	1.000
5:115144699:A:T	C224S	1.000
5:115144733:G:C	C212W	1.000
5:115144734:C:G	C212S	1.000
5:115144734:C:T	C212Y	1.000
5:115144735:A:G	C212R	1.000
5:115144735:A:T	C212S	1.000
5:115147134:G:C	H187D	1.000
5:115147149:A:G	C182R	1.000

dbSNP variants (sampled 300 via entrez): RS1000010725 (5:115138146 C>G,T), RS1000028017 (5:115171772 T>C), RS1000099275 (5:115181845 A>AT), RS1000132458 (5:115166740 C>A,T), RS1000209308 (5:115162750 G>C), RS1000264602 (5:115132591 A>C,G), RS1000304134 (5:115182093 C>G), RS1000324929 (5:115131033 A>G), RS1000365413 (5:115136200 T>C), RS1000373225 (5:115126294 A>G), RS1000389963 (5:115177240 C>G), RS1000404331 (5:115126544 G>A), RS1000447861 (5:115172062 T>C), RS1000468233 (5:115152069 T>A), RS1000581436 (5:115158391 G>C)

Disease associations

OMIM: gene MIM:609317 | disease phenotypes: MIM:206500

GenCC curated gene-disease

Disease	Classification	Inheritance
anencephaly 1	Limited	Unknown

Mondo (2): anencephaly 1 (MONDO:0008791), anencephaly (MONDO:0000819)

Orphanet (1): Isolated anencephaly/exencephaly (Orphanet:1048)

HPO phenotypes

4 total (4 of 4 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0002323	Anencephaly
HP:0002414	Spina bifida
HP:0003577	Congenital onset

GWAS associations

21 associations (top):

Study	Trait	p-value
GCST004776_21	Systolic blood pressure	4.000000e-06
GCST004777_7	Diastolic blood pressure	2.000000e-06
GCST006166_57	Diastolic blood pressure x alcohol consumption interaction (2df test)	5.000000e-10
GCST006166_91	Diastolic blood pressure x alcohol consumption interaction (2df test)	2.000000e-14
GCST006167_50	Mean arterial pressure x alcohol consumption interaction (2df test)	8.000000e-12
GCST006187_13	Diastolic blood pressure (cigarette smoking interaction)	2.000000e-17
GCST006188_28	Systolic blood pressure (cigarette smoking interaction)	2.000000e-17
GCST006258_30	Diastolic blood pressure	4.000000e-11
GCST006259_37	Systolic blood pressure	2.000000e-10
GCST007094_25	Diastolic blood pressure	7.000000e-09
GCST007095_116	Systolic blood pressure	2.000000e-08
GCST007095_117	Systolic blood pressure	3.000000e-07
GCST007098_17	Diastolic blood pressure	4.000000e-08
GCST007098_18	Diastolic blood pressure	2.000000e-06
GCST007099_107	Systolic blood pressure	2.000000e-10
GCST007704_118	Diastolic blood pressure	6.000000e-06
GCST007706_135	Mean arterial pressure	3.000000e-06
GCST007706_137	Mean arterial pressure	5.000000e-06
GCST010725_86	Malaria	2.000000e-06
GCST010725_92	Malaria	7.000000e-06
GCST90013421_34	Left-handedness	3.000000e-11

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0006335	systolic blood pressure
EFO:0006336	diastolic blood pressure
EFO:0004329	alcohol drinking
EFO:0006340	mean arterial pressure
EFO:0006527	smoking status measurement
EFO:0009902	handedness

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D000757	Anencephaly	C10.500.680.196; C16.131.085.197; C16.131.666.680.196

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
trichostatin A	affects cotreatment, decreases expression	3
(+)-JQ1 compound	increases expression	3
sodium arsenite	increases expression	2
Benzo(a)pyrene	affects methylation, increases expression, increases methylation	2
Cisplatin	increases expression, affects cotreatment, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Tretinoin	decreases expression	2
Aflatoxin B1	decreases methylation, increases methylation	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
propionaldehyde	increases expression	1
arsenite	increases methylation	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
butyraldehyde	increases expression	1
potassium chromate(VI)	increases expression	1
coumarin	increases phosphorylation	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment	1
pentanal	increases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
licochalcone B	increases expression	1
jinfukang	decreases expression, affects cotreatment	1
NSC 689534	increases expression, affects binding	1
theaflavin-3,3’-digallate	affects expression	1
Air Pollutants	increases abundance, increases expression	1
Aldehydes	increases expression	1
Amiodarone	increases expression	1
Arsenic	affects methylation	1
Atrazine	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00031122	Not specified	UNKNOWN	Study of Genetic Risk Factors for Spina Bifida and Anencephaly
NCT00636233	Not specified	COMPLETED	Genetics of Spina Bifida and Anencephaly