ZSWIM2

Summary

ZSWIM2 (zinc finger SWIM-type containing 2, HGNC:30990) is a protein-coding gene on chromosome 2q32.1, encoding E3 ubiquitin-protein ligase ZSWIM2 (Q8NEG5). E3 ubiquitin-protein ligase involved in the regulation of Fas-, DR3- and DR4-mediated apoptosis.

Predicted to enable ubiquitin protein ligase activity and zinc ion binding activity. Predicted to be involved in apoptotic process and protein polyubiquitination. Predicted to act upstream of or within positive regulation of extrinsic apoptotic signaling pathway via death domain receptors.

Source: NCBI Gene 151112 — automated summary from GO annotations (Alliance of Genome Resources).

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 85 total
• GTEx eGene: eQTL in 10 tissues, sQTL in 1 (q < 0.05)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.06 (unconstrained)
• MANE Select transcript: NM_182521
• Notable: 85 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30990
Approved symbol	ZSWIM2
Name	zinc finger SWIM-type containing 2
Location	2q32.1
Locus type	gene with protein product
Status	Approved
Aliases	MGC33890, ZZZ2, MEX
Ensembl gene	ENSG00000163012
Ensembl biotype	protein_coding
Entrez	151112

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 nonsense_mediated_decay

MANE Select: ENST00000295131

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 5: 1

ENST00000295131, ENST00000419862, ENST00001138065

RefSeq mRNA: 1 — MANE Select: NM_182521 NM_182521

CCDS: CCDS33348

Canonical transcript exons

ENST00000295131 — 9 exons

Exon	Start	End
ENSE00001070635	186827475	186828790
ENSE00001070637	186833946	186834030
ENSE00001070639	186848966	186849170
ENSE00001070640	186833120	186833232
ENSE00001070641	186838959	186839169
ENSE00001070642	186829727	186829880
ENSE00001130202	186837306	186837554
ENSE00001241066	186844717	186844757
ENSE00003506878	186847719	186847795

Expression profiles

Bgee: expression breadth broad, 61 present calls, max score 88.60.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0196 / max 12.6304, expressed in 5 samples.

Highest expression (Bgee): male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad, testis, sperm, adenohypophysis.

Genetic regulation across tissues (GTEx eQTL / sQTL)

ZSWIM2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 10 tissues and its splicing (sQTL) in 1 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

11 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Testis	sqtl	1.3e-13	+0.61	2:186850731:C:T
Testis	eqtl	7.3e-11	+0.19	2:186852402:T:C
Adipose Visceral Omentum	eqtl	2.2e-07	-0.34	2:186842713:C:A
Cells Cultured fibroblasts	eqtl	2.2e-07	-0.19	2:186850731:C:T
Adipose Subcutaneous	eqtl	1.3e-05	-0.27	2:186824351:C:T
Pituitary	eqtl	3.0e-04	-0.33	2:186843992:C:T
Brain Nucleus accumbens basal ganglia	eqtl	3.0e-04	-0.44	2:186840395:A:G
Brain Cortex	eqtl	5.8e-04	-0.78	2:186870952:A:G
Brain Caudate basal ganglia	eqtl	1.3e-03	-0.39	2:186825547:C:G
Brain Frontal Cortex BA9	eqtl	1.3e-02	-0.46	2:186846434:T:G
Brain Putamen basal ganglia	eqtl	4.1e-02	+0.72	2:187005848:A:G

FANTOM5 promoters

2 alternative TSS:

Promoter ID	TPM avg	Samples expressed
32793	0.0128	5
32794	0.0069	3

Top tissues by expression

showing 100 of 222 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	88.60	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	66.55	gold quality
left testis	UBERON:0004533	66.49	gold quality
testis	UBERON:0000473	65.92	gold quality
right testis	UBERON:0004534	65.19	gold quality
sperm	CL:0000019	65.12	silver quality
adenohypophysis	UBERON:0002196	56.38	gold quality
pituitary gland	UBERON:0000007	55.59	gold quality
buccal mucosa cell	CL:0002336	54.37	silver quality
lower lobe of lung	UBERON:0008949	50.79	silver quality
prefrontal cortex	UBERON:0000451	48.50	gold quality
cortical plate	UBERON:0005343	48.33	gold quality
Brodmann (1909) area 9	UBERON:0013540	46.22	gold quality
hypothalamus	UBERON:0001898	45.69	gold quality
nucleus accumbens	UBERON:0001882	45.53	gold quality
cardia of stomach	UBERON:0001162	45.46	gold quality
frontal cortex	UBERON:0001870	44.50	gold quality
stromal cell of endometrium	CL:0002255	44.37	gold quality
neocortex	UBERON:0001950	43.85	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	43.37	gold quality
forebrain	UBERON:0001890	43.30	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	42.62	gold quality
secondary oocyte	CL:0000655	42.57	gold quality
cerebral cortex	UBERON:0000956	42.53	gold quality
anterior cingulate cortex	UBERON:0009835	42.24	gold quality
right frontal lobe	UBERON:0002810	41.95	gold quality
vastus lateralis	UBERON:0001379	41.41	gold quality
quadriceps femoris	UBERON:0001377	41.37	gold quality
superficial temporal artery	UBERON:0001614	41.33	gold quality
islet of Langerhans	UBERON:0000006	41.12	gold quality
palpebral conjunctiva	UBERON:0001812	41.10	gold quality
caudate nucleus	UBERON:0001873	41.03	gold quality
brain	UBERON:0000955	41.00	gold quality
mucosa of paranasal sinus	UBERON:0005030	40.98	gold quality
amniotic fluid	UBERON:0000173	40.69	gold quality
jejunal mucosa	UBERON:0000399	40.59	gold quality
biceps brachii	UBERON:0001507	40.57	gold quality
epithelium of nasopharynx	UBERON:0001951	40.45	gold quality
myocardium	UBERON:0002349	40.45	gold quality
gingival epithelium	UBERON:0001949	40.43	gold quality
germinal epithelium of ovary	UBERON:0001304	40.33	gold quality
esophagus squamous epithelium	UBERON:0006920	40.29	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	40.27	gold quality
jejunum	UBERON:0002115	40.18	gold quality
placenta	UBERON:0001987	40.11	gold quality
mammary duct	UBERON:0001765	40.07	gold quality
cartilage tissue	UBERON:0002418	40.06	gold quality
ventricular zone	UBERON:0003053	40.03	gold quality
oviduct epithelium	UBERON:0004804	40.03	gold quality
primary visual cortex	UBERON:0002436	40.02	silver quality
mucosa of sigmoid colon	UBERON:0004993	39.95	gold quality
occipital lobe	UBERON:0002021	39.94	silver quality
deltoid	UBERON:0001476	39.83	gold quality
saphenous vein	UBERON:0007318	39.83	gold quality
parotid gland	UBERON:0001831	39.81	gold quality
oocyte	CL:0000023	39.80	gold quality
urethra	UBERON:0000057	39.80	gold quality
heart right ventricle	UBERON:0002080	39.79	gold quality
Ammon’s horn	UBERON:0001954	39.77	silver quality
pericardium	UBERON:0002407	39.77	gold quality
layer of synovial tissue	UBERON:0007616	39.77	gold quality
endothelial cell	CL:0000115	39.75	gold quality
synovial joint	UBERON:0002217	39.70	gold quality
dorsal root ganglion	UBERON:0000044	39.68	gold quality
nipple	UBERON:0002030	39.68	gold quality
bronchial epithelial cell	CL:0002328	39.65	gold quality
decidua	UBERON:0002450	39.65	gold quality
penis	UBERON:0000989	39.64	gold quality
gingiva	UBERON:0001828	39.64	gold quality
bronchus	UBERON:0002185	39.64	gold quality
trigeminal ganglion	UBERON:0001675	39.63	gold quality
tendon of biceps brachii	UBERON:0008188	39.60	gold quality
inferior vagus X ganglion	UBERON:0005363	39.57	gold quality
superior surface of tongue	UBERON:0007371	39.56	gold quality
pylorus	UBERON:0001166	39.55	gold quality
renal medulla	UBERON:0000362	39.53	gold quality
pons	UBERON:0000988	39.51	gold quality
putamen	UBERON:0001874	39.50	gold quality
thymus	UBERON:0002370	39.50	gold quality
medulla oblongata	UBERON:0001896	39.48	gold quality
superior vestibular nucleus	UBERON:0007227	39.47	gold quality
colonic mucosa	UBERON:0000317	39.45	gold quality
parietal pleura	UBERON:0002400	39.45	gold quality
Brodmann (1909) area 23	UBERON:0013554	39.40	gold quality
dorsal plus ventral thalamus	UBERON:0001897	39.38	gold quality
tongue	UBERON:0001723	39.37	gold quality
cerebellar vermis	UBERON:0004720	39.37	gold quality
oral cavity	UBERON:0000167	39.35	gold quality
subthalamic nucleus	UBERON:0001906	39.35	gold quality
superior frontal gyrus	UBERON:0002661	39.35	silver quality
ventral tegmental area	UBERON:0002691	39.35	gold quality
trachea	UBERON:0003126	39.33	gold quality
parietal lobe	UBERON:0001872	39.32	gold quality
vena cava	UBERON:0004087	39.31	gold quality
pharyngeal mucosa	UBERON:0000355	39.27	gold quality
substantia nigra pars compacta	UBERON:0001965	39.23	gold quality
visceral pleura	UBERON:0002401	39.23	gold quality
postcentral gyrus	UBERON:0002581	39.23	gold quality
body of tongue	UBERON:0011876	39.22	gold quality
medial globus pallidus	UBERON:0002477	39.18	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.92

HPA expression

RNA tissue specificity: Tissue enriched

35 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM
Testis	tissue	8.7
Periaqueductal gray	tissue	4.0
Basal ganglia	tissue	2.1
Hippocampal formation	tissue	1.6
Septum	tissue	1.6
Amygdala	tissue	1.5
Cerebral cortex	tissue	1.4
Hypothalamus	tissue	1.4
Olfactory bulb	tissue	1.4
Insular cortex	tissue	1.4
Pons	tissue	1.3
Retrosplenial cortex	tissue	1.3
Entorhinal cortex	tissue	1.2
Somatosensory cortex	tissue	1.2
Occipital cortex	tissue	1.2
Prefrontal cortex	tissue	1.1
Cerebellum	tissue	1.1
Ventral forebrain	tissue	1.1
Retrosplenial and cingulate cortex	tissue	1.1
Temporal cortex	tissue	1.1
Corpus callosum	tissue	1.0
Motor cortex	tissue	0.9
Midbrain	tissue	0.8
Medulla oblongata	tissue	0.8
Thalamus	tissue	0.8
Putamen	tissue	0.7
Pituitary gland	tissue	0.6
Superior colliculi	tissue	0.6
Substantia nigra	tissue	0.6
Spinal cord	tissue	0.5
Nucleus accumbens	tissue	0.2
Locus coeruleus	tissue	0.2
Choroid plexus	tissue	0.1
Hippocampus	tissue	0.1
Postcentral gyrus	tissue	0.1

Brain sub-regions (HPA Brain Atlas): detected in 146; highest nTPM — Dorsal hippocampus (1.6), Subiculum (1.4), Ventral hippocampus (1.4), White matter (1.0), Arcuate nucleus (0.6).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting ZSWIM2 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 36 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-7856-5P	99.75	69.99	2901
HSA-MIR-6073	99.60	70.36	793
HSA-MIR-3942-3P	99.57	69.03	2854
HSA-MIR-12123	99.52	71.79	2990
HSA-MIR-6083	99.47	68.73	2393
HSA-MIR-6080	99.43	69.43	373
HSA-MIR-3140-5P	99.39	69.04	1136
HSA-MIR-329-5P	99.27	68.11	1597
HSA-MIR-664A-3P	99.22	71.08	2696
HSA-MIR-5190	99.15	67.76	1234
HSA-MIR-4464	98.95	67.73	820
HSA-MIR-4748	98.95	67.53	810
HSA-MIR-138-2-3P	98.91	68.33	1643
HSA-MIR-6074	98.89	69.64	2187

Functional genomics

gnomAD constraint: pLI 8.18e-08, LOEUF 1.06, missense Z -0.344 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000295131 — one region, missense o/e 1.06.

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	zswim2	ENSDARG00000075700
mus_musculus	Zswim2	ENSMUSG00000034552
rattus_norvegicus	Zswim2	ENSRNOG00000032579

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Arabidopsis thaliana	F4HZZ4	82.7%	Diamond
Oryza sativa Japonica Group	Q10R93	69.1%	Diamond
Schizosaccharomyces pombe 972h-	Q9P7E1	58.7%	Diamond
Encephalitozoon cuniculi GB-M1	Q8SV35	58.1%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
CALCRL	protein-coding	10203
FAM171B	protein-coding	165215
TFPI	protein-coding	7035
CALCRL-AS1	ncRNA	105373786
ITGAV	protein-coding	3685

Protein

Protein identifiers

E3 ubiquitin-protein ligase ZSWIM2 — Q8NEG5 (reviewed: Q8NEG5)

Alternative names: MEKK1-related protein X, RING-type E3 ubiquitin transferase ZSWIM2, ZZ-type zinc finger-containing protein 2, Zinc finger SWIM domain-containing protein 2

All UniProt accessions (2): Q8NEG5, F8WCC6

UniProt curated annotations — full annotation on UniProt →

Function. E3 ubiquitin-protein ligase involved in the regulation of Fas-, DR3- and DR4-mediated apoptosis. Functions in conjunction with the UBE2D1, UBE2D3 and UBE2E1 E2 ubiquitin-conjugating enzymes.

Subunit / interactions. Dimer. Interacts with UBE2D1.

Tissue specificity. Expression is testis-specific.

Post-translational modifications. Polyubiquitinated. Polyubiquitination is followed by degradation via the proteasome.

Domain organisation. The SWIM-type zinc finger is required for ubiquitination activity.

RefSeq proteins (1): NP_872327* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000433	Znf_ZZ	Domain
IPR001841	Znf_RING	Domain
IPR007527	Znf_SWIM	Domain
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR039903	Zswim2	Family
IPR043145	Znf_ZZ_sf	Homologous_superfamily

Pfam: PF00569, PF04434, PF13639

UniProt features (27 total): binding site 8, sequence conflict 7, strand 5, zinc finger region 4, helix 2, chain 1

Structure

Experimental structures (PDB)

1 structures by resolution:

PDB	Title	Method	Resolution (Å)
2DIP	Solution structure of the ZZ domain of Zinc finger SWIM domain containing protein 2	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NEG5-F1	63.82	0.36

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Transferases, Metabolic proteins, Predicted intracellular proteins, Plasma proteins

Protein evidence: Evidence at protein level

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 (8)

Position	Role
261	Zn(2+)
267	Zn(2+)
270	Zn(2+)
234	Zn(2+)
237	Zn(2+)
249	Zn(2+)
252	Zn(2+)
258	Zn(2+)

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 0; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

MSigDB gene sets: 57 (showing top): GOBP_EXTRINSIC_APOPTOTIC_SIGNALING_PATHWAY, GOBP_REGULATION_OF_EXTRINSIC_APOPTOTIC_SIGNALING_PATHWAY_VIA_DEATH_DOMAIN_RECEPTORS, GOBP_APOPTOTIC_SIGNALING_PATHWAY, GOBP_REGULATION_OF_EXTRINSIC_APOPTOTIC_SIGNALING_PATHWAY, GOBP_EXTRINSIC_APOPTOTIC_SIGNALING_PATHWAY_VIA_DEATH_DOMAIN_RECEPTORS, GOBP_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, GOBP_PROTEIN_POLYUBIQUITINATION, MYB_Q3, GOBP_POSITIVE_REGULATION_OF_EXTRINSIC_APOPTOTIC_SIGNALING_PATHWAY, GOBP_POSITIVE_REGULATION_OF_EXTRINSIC_APOPTOTIC_SIGNALING_PATHWAY_VIA_DEATH_DOMAIN_RECEPTORS, GOBP_POSITIVE_REGULATION_OF_APOPTOTIC_SIGNALING_PATHWAY, MYB_Q5_01, GOBP_REGULATION_OF_APOPTOTIC_SIGNALING_PATHWAY, GOMF_ACYLTRANSFERASE_ACTIVITY, GOMF_AMINOACYLTRANSFERASE_ACTIVITY

GO Biological Process (2): protein polyubiquitination (GO:0000209), apoptotic process (GO:0006915)

GO Molecular Function (5): zinc ion binding (GO:0008270), ubiquitin protein ligase activity (GO:0061630), ubiquitin-protein transferase activity (GO:0004842), transferase activity (GO:0016740), metal ion binding (GO:0046872)

GO top-level categories

10 GO namespaces:

Category	Terms
protein ubiquitination	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
transition metal ion binding	1
ubiquitin-protein transferase activity	1
ubiquitin-like protein ligase activity	1
ubiquitin-like protein transferase activity	1
catalytic activity	1
cation binding	1

Protein interactions and networks

STRING

showing 15 of 668 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZSWIM2	RNF148	Q8N7C7	583
ZSWIM2	CCDC146	Q8IYE0	530
ZSWIM2	RNF151	Q2KHN1	529
ZSWIM2	TSNAXIP1	Q2TAA8	497
ZSWIM2	RSPH14	Q9UHP6	481
ZSWIM2	OXNAD1	Q96HP4	467
ZSWIM2	ZSWIM7	Q19AV6	466
ZSWIM2	RSPH10B	P0C881	461
ZSWIM2	SCP2D1	Q9UJQ7	457
ZSWIM2	TRIML1	Q8N9V2	446
ZSWIM2	SLC66A1	Q6ZP29	436
ZSWIM2	CFAP161	Q6P656	430
ZSWIM2	LRRC23	Q53EV4	421
ZSWIM2	RNF150	Q9ULK6	420
ZSWIM2	RNF133	Q8WVZ7	410

IntAct

Human interaction partners of ZSWIM2 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

5 partners by confidence:

Partner	Interaction type	MIscore	Records
SEMG1	association	0.530	2
EZR	physical association	0.400	1
ECE1	physical association	0.370	1
MAGEA11	physical association	0.370	1
UBE2U	physical association	0.370	1

BioGRID (16 interactions; top human partners by supporting records): BCAM (Affinity Capture-MS; 2 records), LRFN4 (Affinity Capture-MS; 2 records), RNASE7 (Affinity Capture-MS; 2 records), SEMG1 (Affinity Capture-MS; 2 records), TKTL2 (Affinity Capture-MS; 2 records), C16orf72 (Positive Genetic), CSK (Synthetic Lethality), EZR (Cross-Linking-MS (XL-MS)), MAGEA11 (Two-hybrid), SET (Cross-Linking-MS (XL-MS)), UBE2U (Two-hybrid)

SIGNOR signaling

5 signaling interactions:

A	Effect	B	Mechanism
Ub:E2	“up-regulates activity”	ZSWIM2	ubiquitination
UBE2D1	“up-regulates activity”	ZSWIM2	binding
UBE2E1	“up-regulates activity”	ZSWIM2	binding
ZSWIM2	up-regulates	Apoptosis
UBE2D3	“up-regulates activity”	ZSWIM2	binding

Disease & clinical

Genetic variants

Variant evidence for ZSWIM2: 85 ClinVar records (0 pathogenic / likely pathogenic); 5 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	77
Likely benign	4
Benign	1

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 32 predictions of 720):

Position(s)	Effect	Δscore	Sites
2:186837317	donor_gain	1.0000
2:186828792	acceptor_gain	0.9900
2:186838957–186838958	donor_loss	0.9900	5
2:186839170–186839171	acceptor_loss	0.9900	6
2:186847717–186847718	donor_loss	0.9900	5
2:186847796–186847797	acceptor_loss	0.9900	6
2:186848788	donor_gain	0.9900
2:186848995	donor_gain	0.9900
2:186849052	donor_gain	0.9900
2:186828791–186828792	acceptor_loss	0.9800	5

AlphaMissense

629 missense substitutions predicted likely pathogenic (of 4,208 scored), across 171 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
H173	8	0.878	0.963
H367	8	0.876	0.947
H78	8	0.838	0.954
H364	8	0.829	0.943
C164	7	0.967	0.984
C147	7	0.958	0.986
C234	7	0.955	0.978
C344	7	0.955	0.983
C150	7	0.953	0.975
C194	7	0.946	0.991
C176	7	0.944	0.981
C197	7	0.936	0.970
C382	7	0.933	0.972
C64	7	0.931	0.962
C347	7	0.929	0.963
C168	7	0.928	0.965
F366	7	0.920	0.985
C76	7	0.907	0.950
C362	7	0.905	0.955
C370	7	0.904	0.947

HPA cancer prognostics

RNA cancer specificity: Not detected

Disease associations

OMIM: gene `` | disease phenotypes:

GWAS associations

5 associations:

Study	Trait	p-value
GCST006624_24	Systolic blood pressure	1e-11
GCST90020026_588	Hip index	2e-9
GCST90020029_894	Waist circumference adjusted for body mass index	1e-8
GCST90020025_100	Waist-to-hip ratio adjusted for BMI	3e-8
GCST90020029_893	Waist circumference adjusted for body mass index	4e-8

EFO canonical traits (from GWAS)

4 canonical traits:

EFO ID	Trait name
EFO:0006335	systolic blood pressure
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008039	BMI-adjusted hip circumference
EFO:0007789	BMI-adjusted waist circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

6 total (human), top 6 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
CGP 52608	affects binding, increases reaction	1
semilicoisoflavone B	decreases phosphorylation	1
Arsenic	increases methylation	1
Benzo(a)pyrene	increases methylation	1
Lead	affects methylation	1
Tobacco Smoke Pollution	decreases expression	1

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.