HECW1

Summary

HECW1 (HECT, C2 and WW domain containing E3 ubiquitin protein ligase 1, HGNC:22195) is a protein-coding gene on chromosome 7p14.1-p13, encoding E3 ubiquitin-protein ligase HECW1 (Q76N89). E3 ubiquitin-protein ligase that mediates ubiquitination and subsequent degradation of DVL1.

Predicted to enable ubiquitin protein ligase activity. Predicted to be involved in regulation of dendrite morphogenesis and ubiquitin-dependent protein catabolic process. Predicted to be located in cytosol. Predicted to be active in cytoplasm.

Source: NCBI Gene 23072 — RefSeq curated summary.

At a glance

• GWAS associations: 12
• Clinical variants (ClinVar): 232 total
• MANE Select transcript: NM_015052

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:22195
Approved symbol	HECW1
Name	HECT, C2 and WW domain containing E3 ubiquitin protein ligase 1
Location	7p14.1-p13
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0322, NEDL1
Ensembl gene	ENSG00000002746
Ensembl biotype	protein_coding
OMIM	610384
Entrez	23072

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 8 protein_coding_CDS_not_defined, 4 protein_coding

ENST00000395891, ENST00000429529, ENST00000453890, ENST00000461842, ENST00000464944, ENST00000471043, ENST00000471527, ENST00000481031, ENST00000490954, ENST00000492310, ENST00000493057, ENST00000857209

RefSeq mRNA: 2 — MANE Select: NM_015052 NM_001287059, NM_015052

CCDS: CCDS5469, CCDS69286

Canonical transcript exons

ENST00000395891 — 30 exons

Exon	Start	End
ENSE00001488227	43112647	43112937
ENSE00001593234	43552222	43552336
ENSE00001597880	43450828	43450929
ENSE00001606426	43554592	43554790
ENSE00001625018	43456297	43456447
ENSE00001635942	43508969	43509121
ENSE00001644198	43541163	43541261
ENSE00001644279	43541869	43541998
ENSE00001673445	43561815	43566001
ENSE00001678628	43463660	43463799
ENSE00001679485	43500699	43500782
ENSE00001706825	43493084	43493180
ENSE00001707285	43550445	43550591
ENSE00001708899	43243875	43243932
ENSE00001726462	43508018	43508131
ENSE00001732068	43479610	43479744
ENSE00001740935	43468920	43469105
ENSE00001750269	43444218	43445570
ENSE00001750459	43507137	43507257
ENSE00001758607	43501213	43501322
ENSE00001759332	43492075	43492180
ENSE00001766960	43466447	43466568
ENSE00001773457	43442529	43442629
ENSE00002265501	43438003	43438145
ENSE00002268386	43114157	43114391
ENSE00003488009	43407562	43407731
ENSE00003521980	43360886	43360980
ENSE00003598940	43396814	43396889
ENSE00003671326	43311763	43312087
ENSE00003677574	43320635	43320742

Expression profiles

Bgee: expression breadth ubiquitous, 172 present calls, max score 93.73.

FANTOM5 (CAGE): breadth broad, TPM avg 3.6338 / max 150.4080, expressed in 509 samples.

FANTOM5 promoters (15 alternative TSS)

Promoter ID	TPM avg	Samples expressed
78339	1.5132	216
78351	0.4565	203
78338	0.3210	89
78346	0.3179	67
78352	0.2937	153
78336	0.2370	87
78347	0.0991	39
78342	0.0837	52
78344	0.0706	33
78337	0.0617	34

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
Brodmann (1909) area 23	UBERON:0013554	93.73	gold quality
middle temporal gyrus	UBERON:0002771	93.19	gold quality
endothelial cell	CL:0000115	91.83	gold quality
primary visual cortex	UBERON:0002436	87.31	gold quality
cortical plate	UBERON:0005343	86.00	gold quality
occipital lobe	UBERON:0002021	84.12	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.60	gold quality
ganglionic eminence	UBERON:0004023	82.89	gold quality
prefrontal cortex	UBERON:0000451	82.83	gold quality
frontal cortex	UBERON:0001870	80.06	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	79.81	gold quality
superior frontal gyrus	UBERON:0002661	79.51	gold quality
pons	UBERON:0000988	79.46	gold quality
neocortex	UBERON:0001950	79.39	gold quality
lateral nuclear group of thalamus	UBERON:0002736	78.87	gold quality
right frontal lobe	UBERON:0002810	78.61	gold quality
Brodmann (1909) area 9	UBERON:0013540	78.39	gold quality
parietal lobe	UBERON:0001872	77.91	gold quality
postcentral gyrus	UBERON:0002581	77.29	gold quality
cerebral cortex	UBERON:0000956	76.99	gold quality
Brodmann (1909) area 46	UBERON:0006483	76.89	silver quality
entorhinal cortex	UBERON:0002728	75.41	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	75.39	gold quality
cingulate cortex	UBERON:0003027	74.98	gold quality
anterior cingulate cortex	UBERON:0009835	74.81	gold quality
pancreatic ductal cell	CL:0002079	74.58	silver quality
buccal mucosa cell	CL:0002336	73.71	silver quality
ventricular zone	UBERON:0003053	73.61	gold quality
embryo	UBERON:0000922	73.53	gold quality
calcaneal tendon	UBERON:0003701	73.31	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-HCAD-25	yes	89.93
E-HCAD-35	yes	69.59
E-ANND-3	yes	7.36

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

102 targeting HECW1, 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-432-3P	100.00	67.86	705
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-3140-3P	99.88	68.47	2069
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-6715A-3P	99.83	68.05	1473
HSA-MIR-4420	99.82	70.08	1624
HSA-MIR-181B-2-3P	99.81	70.06	1646
HSA-MIR-181B-3P	99.81	70.06	1646
HSA-MIR-204-5P	99.79	71.62	2439
HSA-MIR-211-5P	99.79	71.65	2440
HSA-MIR-5002-5P	99.76	70.84	1763
HSA-MIR-623	99.76	68.16	1170

Literature-anchored findings (GeneRIF, showing 12)

• interaction among misfolded SOD1, NEDL1, translocon-associated protein-delta, and Dishevelled-1 forms a ubiquitinated protein complex that is included in potentially cytotoxic protein aggregates (PMID:14684739)
• functional interaction of NEDL1 with p53 might contribute to the induction of apoptosis in cancerous cells bearing wild-type p53. (PMID:18223681)
• These findings suggest that the human NEDL1 transgenic mice might develop Amyotrophic lateral sclerosis-like symptoms, showing signs of motor abnormalities, accompanied with significant reduction in muscle strength. (PMID:20976258)
• These findings suggest that RNF43 is associated with p53-mediated apoptosis in collaboration with NEDL1 in colorectal carcinogenesis. (PMID:21108931)
• Ndel1 regulates Dyn2 GTPase activity and impacts GluR1-containing membranes distribution in a manner reminiscent of Dyn2. (PMID:21283621)
• Ndel1 acts as a novel upstream regulator of the trichoplein-Aurora A pathway to inhibit primary cilia assembly. (PMID:26880200)
• The ubiquitin E3 ligase HECW1 catalyzes TTF1 ubiquitination. (PMID:30849519)
• Study reported for the first time that HECW1 mRNA levels were negatively correlated with Gd-IgA1 levels and pointed to a new regulatory mechanism of IgA nephropathy that can explain the aberrant glycosylation of IgA1. (PMID:31057023)
• E3 ubiquitin ligase HECW1 promotes the metastasis of non-small cell lung cancer cells through mediating the ubiquitination of Smad4. (PMID:33529121)
• Integrating HECW1 expression into the clinical indicators exhibits high accuracy in assessing the prognosis of patients with clear cell renal cell carcinoma. (PMID:34348693)
• Study of Ubiquitin Pathway Genes in a French Population with Amyotrophic Lateral Sclerosis: Focus on HECW1 Encoding the E3 Ligase NEDL1. (PMID:36674783)
• HECW1 induces NCOA4-regulated ferroptosis in glioma through the ubiquitination and degradation of ZNF350. (PMID:38049396)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	hecw1b	ENSDARG00000004291
danio_rerio	HECW1	ENSDARG00000100958
mus_musculus	Hecw1	ENSMUSG00000021301
rattus_norvegicus	Hecw1	ENSRNOG00000016046

Paralogs (24): UBE3C (ENSG00000009335), NEDD4L (ENSG00000049759), NEDD4 (ENSG00000069869), ITCH (ENSG00000078747), HACE1 (ENSG00000085382), HUWE1 (ENSG00000086758), HECTD1 (ENSG00000092148), UBR5 (ENSG00000104517), SMURF2 (ENSG00000108854), UBE3A (ENSG00000114062), AREL1 (ENSG00000119682), WWP1 (ENSG00000123124), HERC2 (ENSG00000128731), HECW2 (ENSG00000138411), HERC3 (ENSG00000138641), HERC6 (ENSG00000138642), HERC5 (ENSG00000138646), HERC4 (ENSG00000148634), UBE3B (ENSG00000151148), TRIP12 (ENSG00000153827), HECTD2 (ENSG00000165338), HECTD4 (ENSG00000173064), WWP2 (ENSG00000198373), SMURF1 (ENSG00000198742)

Protein

Protein identifiers

E3 ubiquitin-protein ligase HECW1 — Q76N89 (reviewed: Q76N89)

Alternative names: HECT, C2 and WW domain-containing protein 1, HECT-type E3 ubiquitin transferase HECW1, NEDD4-like E3 ubiquitin-protein ligase 1

All UniProt accessions (2): Q76N89, H7C3Q2

UniProt curated annotations — full annotation on UniProt →

Function. E3 ubiquitin-protein ligase that mediates ubiquitination and subsequent degradation of DVL1. Also targets the mutant SOD1 protein involved in familial amyotrophic lateral sclerosis (FALS). Forms cytotoxic aggregates with DVL1, SSR3 and mutant SOD1 that lead to motor neuron death in FALS.

Subunit / interactions. Interacts with DVL1 and SSR3. Also interacts with mutant SOD1.

Subcellular location. Cytoplasm.

Tissue specificity. Predominantly expressed in neurons of adult and fetal brain. Weakly expressed in the kidney.

Pathway. Protein modification; protein ubiquitination.

Isoforms (2)

UniProt ID	Names	Canonical?
Q76N89-1	1	yes
Q76N89-2	2

RefSeq proteins (2): NP_001273988, NP_055867* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000008	C2_dom	Domain
IPR000569	HECT_dom	Domain
IPR001202	WW_dom	Domain
IPR032348	HECW_N	Domain
IPR035892	C2_domain_sf	Homologous_superfamily
IPR035983	Hect_E3_ubiquitin_ligase	Homologous_superfamily
IPR036020	WW_dom_sf	Homologous_superfamily
IPR037795	C2_HECW	Domain
IPR040524	HECW1_helix	Domain
IPR050409	E3_ubiq-protein_ligase	Family

Pfam: PF00168, PF00397, PF00632, PF16562, PF18436

Enzyme classification (BRENDA):

• EC 2.3.2.26 — HECT-type E3 ubiquitin transferase (BRENDA: 14 organisms, 64 substrates, 19 inhibitors, 5 Km, 5 kcat entries)

Substrate kinetics (BRENDA)

1 substrates with measured Km, best-characterized 1. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
[UBC5B]-L-LYSINE	0.0046–0.037	5

UniProt features (36 total): compositionally biased region 9, helix 6, region of interest 5, domain 4, modified residue 3, strand 3, chain 1, coiled-coil region 1, active site 1, splice variant 1, sequence conflict 1, turn 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
3L4H	X-RAY DIFFRACTION	1.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q76N89-F1	61.55	0.26

Functional residue map

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

Catalytic / active sites (1): 1574 (glycyl thioester intermediate)

Post-translational modifications (3): 874, 937, 939

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-4641258	Degradation of DVL

MSigDB gene sets: 118 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_DN, GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_DN, GOBP_DENDRITE_DEVELOPMENT, TGGTGCT_MIR29A_MIR29B_MIR29C, ATACCTC_MIR202, GOBP_REGULATION_OF_DENDRITE_MORPHOGENESIS, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_NEUROGENESIS, GOBP_REGULATION_OF_WNT_SIGNALING_PATHWAY, GOBP_REGULATION_OF_CELL_PROJECTION_ORGANIZATION, GOBP_CANONICAL_WNT_SIGNALING_PATHWAY, GOBP_DENDRITE_MORPHOGENESIS, GOBP_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, GOBP_REGULATION_OF_NEURON_PROJECTION_DEVELOPMENT, GOBP_CELL_PROJECTION_ORGANIZATION

GO Biological Process (4): ubiquitin-dependent protein catabolic process (GO:0006511), protein ubiquitination (GO:0016567), regulation of dendrite morphogenesis (GO:0048814), negative regulation of canonical Wnt signaling pathway (GO:0090090)

GO Molecular Function (4): ubiquitin protein ligase activity (GO:0061630), ubiquitin-protein transferase activity (GO:0004842), protein binding (GO:0005515), transferase activity (GO:0016740)

GO Cellular Component (2): cytoplasm (GO:0005737), cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
TCF dependent signaling in response to WNT	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
protein ubiquitination	1
modification-dependent protein catabolic process	1
protein modification by small protein conjugation	1
regulation of anatomical structure morphogenesis	1
dendrite morphogenesis	1
regulation of dendrite development	1
negative regulation of Wnt signaling pathway	1
canonical Wnt signaling pathway	1
regulation of canonical Wnt signaling pathway	1
ubiquitin-protein transferase activity	1
ubiquitin-like protein ligase activity	1
ubiquitin-like protein transferase activity	1
binding	1
catalytic activity	1
intracellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

1430 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HECW1	SSR4	P51571	887
HECW1	NDFIP1	Q9BT67	823
HECW1	DVL1	O14640	791
HECW1	SOD1	P00441	747
HECW1	UBE2K	P27924	598
HECW1	RNF43	Q68DV7	585
HECW1	UBE2S	Q16763	564
HECW1	NEDD8	Q15843	554
HECW1	PTEN	P60484	506
HECW1	A0A087WY85	A0A087WY85	479
HECW1	RHOBTB3	O94955	446
HECW1	WNT1	P04628	445
HECW1	AGBL3	Q8NEM8	432
HECW1	ST8SIA1	Q92185	428
HECW1	ZC3H12C	Q9C0D7	427

IntAct

28 interactions, top by confidence:

A	B	Type	Score
ARRDC3	WWP2	psi-mi:“MI:0914”(association)	0.770
LDLRAD4	NEDD4	psi-mi:“MI:0914”(association)	0.690
VAX1	HECW1	psi-mi:“MI:0915”(physical association)	0.560
LDLRAD4	WWP2	psi-mi:“MI:0914”(association)	0.530
ENTREP3	NEDD4	psi-mi:“MI:0914”(association)	0.530
PRRG4	HECW1	psi-mi:“MI:0407”(direct interaction)	0.440
HECW1	FBXL15	psi-mi:“MI:0915”(physical association)	0.400
HECW1		psi-mi:“MI:0915”(physical association)	0.370
HECW1	SHANK3	psi-mi:“MI:0915”(physical association)	0.370
HECW1	TSC1	psi-mi:“MI:0915”(physical association)	0.370
CACNA1A	HECW1	psi-mi:“MI:0915”(physical association)	0.370
MPHOSPH8	HCFC1	psi-mi:“MI:0914”(association)	0.350
FAM189B	KLRG2	psi-mi:“MI:0914”(association)	0.350
LDLRAD4	WWP2	psi-mi:“MI:0914”(association)	0.350
TMEM171	STX6	psi-mi:“MI:0914”(association)	0.350
ZNF707	LRP4	psi-mi:“MI:0914”(association)	0.350
ILDR1	FBP1	psi-mi:“MI:0914”(association)	0.350
PRRG1	GGCX	psi-mi:“MI:0914”(association)	0.350
CUEDC1	WWP2	psi-mi:“MI:0914”(association)	0.350
DLG3	KIF1B	psi-mi:“MI:0914”(association)	0.350
ENTREP3	WWP2	psi-mi:“MI:0914”(association)	0.350
HECW1	VAX1	psi-mi:“MI:0915”(physical association)	0.000
GFI1B	HECW1	psi-mi:“MI:0915”(physical association)	0.000
USP7	HECW1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (44): HECW1 (Affinity Capture-MS), HECW1 (Affinity Capture-MS), UBC (Biochemical Activity), UBE2D1 (Reconstituted Complex), UBE2D2 (Reconstituted Complex), UBE2D3 (Reconstituted Complex), UBE2L3 (Reconstituted Complex), HECW1 (Biochemical Activity), UBE2J2 (Reconstituted Complex), DVL1 (Two-hybrid), HECW1 (Affinity Capture-MS), HECW1 (Affinity Capture-MS), HECW1 (PCA), HECW1 (Affinity Capture-Western), HECW1 (Affinity Capture-Western)

ESM2 similar proteins: A0A1B0GTS1, A0A1B0GWH4, A1A4L6, A1YGI6, A6NDR6, B8QB46, F1MJR8, F1QDF8, O35892, O35893, P09015, P15036, P15037, P23497, P52729, P59598, Q32NH9, Q3KRF1, Q3UM89, Q4G112, Q4V7E1, Q5M7N6, Q5ND04, Q5XIV2, Q5ZHX5, Q66IG8, Q6P1R3, Q6PCX9, Q6PJQ5, Q708W2, Q76I76, Q76I79, Q76N89, Q7M6U3, Q8AXQ4, Q8BVK9, Q8IUE0, Q8IUE1, Q8IWB6, Q8IXJ9

Diamond homologs: A0A8C0NGY6, A1CQG2, A1D3C5, A2A5Z6, A2QQ28, A9JRZ0, B0XQ72, B8N7E5, D3ZBM7, D6C652, E1B7Q7, E1C656, F1LP64, F1N6G5, F8W2M1, G0S9J5, G5E870, H2LBU8, O00308, O08759, O13834, O14326, O15033, P39940, P40985, P46934, P46935, P46937, P46938, P51593, P53119, Q03280, Q05086, Q08CZ0, Q09291, Q0CCL1, Q14669, Q15034, Q15386, Q1K9C4

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
Ub:E2	“up-regulates activity”	HECW1	ubiquitination
HECW1	“down-regulates quantity by destabilization”	DVL1	ubiquitination

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	198
Likely benign	3
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

8285 predictions. Top by Δscore:

Variant	Effect	Δscore
7:43138287:GCT:G	donor_gain	1.0000
7:43219518:G:GG	donor_gain	1.0000
7:43312048:G:GT	donor_gain	1.0000
7:43312085:TTG:T	donor_gain	1.0000
7:43312085:TTGG:T	donor_loss	1.0000
7:43312086:TGG:T	donor_loss	1.0000
7:43312088:GTG:G	donor_loss	1.0000
7:43312089:T:G	donor_loss	1.0000
7:43312090:GAG:G	donor_loss	1.0000
7:43320611:T:TA	acceptor_gain	1.0000
7:43320624:T:TA	acceptor_gain	1.0000
7:43320625:G:A	acceptor_gain	1.0000
7:43320632:T:G	acceptor_gain	1.0000
7:43320632:TA:T	acceptor_loss	1.0000
7:43320633:A:AG	acceptor_gain	1.0000
7:43320633:AGAT:A	acceptor_gain	1.0000
7:43320634:G:GA	acceptor_gain	1.0000
7:43320634:GA:G	acceptor_gain	1.0000
7:43320634:GAT:G	acceptor_gain	1.0000
7:43320634:GATG:G	acceptor_gain	1.0000
7:43320634:GATGA:G	acceptor_gain	1.0000
7:43320738:GGAAC:G	donor_gain	1.0000
7:43320739:GAAC:G	donor_gain	1.0000
7:43320739:GAACG:G	donor_gain	1.0000
7:43320740:A:T	donor_gain	1.0000
7:43320740:AAC:A	donor_gain	1.0000
7:43320741:AC:A	donor_gain	1.0000
7:43320741:ACG:A	donor_loss	1.0000
7:43320742:CGT:C	donor_loss	1.0000
7:43320743:G:GG	donor_gain	1.0000

AlphaMissense

10572 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:43311977:T:A	L81H	1.000
7:43311977:T:C	L81P	1.000
7:43312033:T:A	W100R	1.000
7:43312033:T:C	W100R	1.000
7:43312034:G:C	W100S	1.000
7:43312035:G:C	W100C	1.000
7:43312035:G:T	W100C	1.000
7:43312040:T:A	I102K	1.000
7:43312063:G:C	D110H	1.000
7:43312064:A:C	D110A	1.000
7:43312064:A:T	D110V	1.000
7:43312066:T:A	W111R	1.000
7:43312066:T:C	W111R	1.000
7:43312070:T:A	I112N	1.000
7:43312072:G:C	G113R	1.000
7:43312073:G:A	G113D	1.000
7:43312078:T:G	Y115D	1.000
7:43320673:C:A	R131S	1.000
7:43320709:T:A	W143R	1.000
7:43320709:T:C	W143R	1.000
7:43360904:T:C	F160S	1.000
7:43360909:T:C	Y162H	1.000
7:43360909:T:G	Y162D	1.000
7:43360912:T:G	Y163D	1.000
7:43360939:G:C	A172P	1.000
7:43360961:T:A	V179D	1.000
7:43407580:T:C	L217S	1.000
7:43407580:T:G	L217W	1.000
7:43407588:G:A	G220R	1.000
7:43407588:G:C	G220R	1.000

dbSNP variants (sampled 300 via entrez): RS1000005560 (7:43328138 T>C), RS1000007825 (7:43269349 G>T), RS1000015538 (7:43417401 A>C,G,T), RS1000023021 (7:43183963 A>T), RS1000027188 (7:43143091 C>T), RS1000027717 (7:43446550 G>A), RS1000033341 (7:43278192 A>G), RS1000048260 (7:43417625 G>A), RS1000049934 (7:43196752 G>A), RS1000058465 (7:43187913 G>A,C), RS1000059528 (7:43114033 T>G), RS1000060676 (7:43547105 C>T), RS1000065344 (7:43221565 T>C,G), RS1000082319 (7:43306480 C>A,T), RS1000084550 (7:43523994 A>G)

Disease associations

OMIM: gene MIM:610384 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

12 associations (top):

Study	Trait	p-value
GCST001762_407	Obesity-related traits	6.000000e-06
GCST001915_44	Alzheimer’s disease (cognitive decline)	1.000000e-06
GCST002560_4	Type 2 diabetes	4.000000e-06
GCST002927_9	Mercury levels	7.000000e-06
GCST003072_4	Cerebrospinal fluid AB1-42 levels	3.000000e-07
GCST003654_12	Bone mineral density (Ward’s triangle area)	5.000000e-06
GCST004159_4	Serum galactose-deficient IgA1 levels	6.000000e-06
GCST004749_18	Lung cancer in ever smokers	7.000000e-06
GCST005851_27	Delirium	5.000000e-06
GCST006535_5	Irritable bowel syndrome	4.000000e-06
GCST008257_4	Diverticular disease	1.000000e-06
GCST009175_8	Caudal anterior-cingulate cortex volume	3.000000e-06

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0003939	energy intake
EFO:0004670	beta-amyloid 1-42 measurement
EFO:0007785	femoral neck bone mineral density
EFO:0009959	diverticular disease

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs10255565	HECW1		0.00	0

CTD chemical–gene interactions

20 total (human), top 20 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases mutagenesis	3
bisphenol A	decreases methylation, increases expression	2
methylmercuric chloride	increases expression	1
ethyl-p-hydroxybenzoate	increases expression	1
sulforaphane	increases expression	1
sodium arsenite	increases expression	1
benzo(e)pyrene	decreases methylation	1
aflatoxin B2	decreases methylation	1
2-palmitoylglycerol	increases expression	1
abrine	decreases expression	1
Bortezomib	increases expression, increases response to substance	1
Resveratrol	affects cotreatment, decreases expression	1
Arsenic	affects methylation	1
Estradiol	affects cotreatment, increases expression	1
Methapyrilene	decreases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Rotenone	decreases expression	1
Thimerosal	increases expression	1
Valproic Acid	increases methylation	1
Aflatoxin B1	increases methylation	1

Clinical trials (associated diseases)

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