HAP1

Summary

HAP1 (huntingtin associated protein 1, HGNC:4812) is a protein-coding gene on chromosome 17q21.2, encoding Huntingtin-associated protein 1 (P54257). Originally identified as neuronal protein that specifically associates with HTT/huntingtin and the binding is enhanced by an expanded polyglutamine repeat within HTT possibly affecting HAP1 interaction properties.

Huntington’s disease (HD), a neurodegenerative disorder characterized by loss of striatal neurons, is caused by an expansion of a polyglutamine tract in the HD protein huntingtin. This gene encodes a protein that interacts with huntingtin, with two cytoskeletal proteins (dynactin and pericentriolar autoantigen protein 1), and with a hepatocyte growth factor-regulated tyrosine kinase substrate. The interactions with cytoskeletal proteins and a kinase substrate suggest a role for this protein in vesicular trafficking or organelle transport. Several alternatively spliced transcript variants encoding different isoforms have been described for this gene.

Source: NCBI Gene 9001 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 147 total
• MANE Select transcript: NM_177977

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4812
Approved symbol	HAP1
Name	huntingtin associated protein 1
Location	17q21.2
Locus type	gene with protein product
Status	Approved
Aliases	HLP, hHLP1, HIP5
Ensembl gene	ENSG00000173805
Ensembl biotype	protein_coding
OMIM	600947
Entrez	9001

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 8 protein_coding

ENST00000310778, ENST00000341193, ENST00000347901, ENST00000393939, ENST00000442364, ENST00000455021, ENST00000458656, ENST00000885828

RefSeq mRNA: 7 — MANE Select: NM_177977 NM_001079870, NM_001079871, NM_001367459, NM_001367460, NM_001367461, NM_001367462, NM_177977

CCDS: CCDS11406, CCDS42338, CCDS42339

Canonical transcript exons

ENST00000347901 — 11 exons

Exon	Start	End
ENSE00001852763	41722640	41725154
ENSE00002433341	41731493	41731559
ENSE00002435668	41725859	41725897
ENSE00002439017	41728201	41728331
ENSE00002464180	41727762	41727836
ENSE00002482246	41727053	41727144
ENSE00002486765	41732230	41732394
ENSE00002496965	41731937	41732118
ENSE00002525773	41732719	41732798
ENSE00002529022	41731638	41731743
ENSE00003897941	41734166	41734643

Expression profiles

Bgee: expression breadth ubiquitous, 176 present calls, max score 88.81.

FANTOM5 (CAGE): breadth broad, TPM avg 2.7059 / max 322.6269, expressed in 498 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
166021	2.7059	498

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
hypothalamus	UBERON:0001898	88.81	gold quality
secondary oocyte	CL:0000655	83.77	gold quality
oocyte	CL:0000023	83.72	gold quality
amygdala	UBERON:0001876	83.61	gold quality
nucleus accumbens	UBERON:0001882	81.80	gold quality
cingulate cortex	UBERON:0003027	81.30	gold quality
anterior cingulate cortex	UBERON:0009835	81.15	gold quality
caudate nucleus	UBERON:0001873	79.97	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	79.93	gold quality
right frontal lobe	UBERON:0002810	79.20	gold quality
triceps brachii	UBERON:0001509	78.79	silver quality
gluteal muscle	UBERON:0002000	78.61	gold quality
putamen	UBERON:0001874	78.51	gold quality
type B pancreatic cell	CL:0000169	78.49	gold quality
olfactory bulb	UBERON:0002264	78.27	gold quality
vastus lateralis	UBERON:0001379	78.08	gold quality
adenohypophysis	UBERON:0002196	77.87	gold quality
endocervix	UBERON:0000458	77.26	gold quality
pituitary gland	UBERON:0000007	77.21	gold quality
quadriceps femoris	UBERON:0001377	77.11	gold quality
forebrain	UBERON:0001890	76.40	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	75.91	gold quality
temporal lobe	UBERON:0001871	75.79	gold quality
diaphragm	UBERON:0001103	75.66	gold quality
substantia nigra	UBERON:0002038	75.62	gold quality
telencephalon	UBERON:0001893	75.57	gold quality
Brodmann (1909) area 9	UBERON:0013540	75.57	gold quality
brain	UBERON:0000955	75.43	gold quality
central nervous system	UBERON:0001017	75.39	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	75.37	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-5061	yes	9.07
E-CURD-135	no	460.81
E-ANND-3	no	3.50

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): APEX1, MNT, RARB, SSB

Literature-anchored findings (GeneRIF, showing 23)

• The combination of siRNA, the SB transposon, and an accurate transgenic mouse model may permit evaluation of this approach in preventing the pathogenesis associated with expression of mutant Htt. (PMID:15737634)
• Study provides genetic and functional evidence that the M441-HAP1 polymorphism modifies the age-at-onset of Huntington’s disease . (PMID:18192679)
• REST/NRSF, dynactin p150(Glued), huntingtin, HAP1, and RILP form a complex involved in the translocation of REST/NRSF into the nucleus and HAP1 controls REST/NRSF cellular localization in neurons (PMID:18922795)
• REVIEW: function of HAP1 (PMID:19262167)
• HAP1 may participate in axonal transport and activity-dependent release of pro-BDNF by interacting with the BDNF prodomain. (PMID:19996106)
• ADORA2A, but not HAP1 or OGG1, may have a role in age at onset in Huntington’s disease (PMID:20512606)
• sortilin stabilizes the proBDNF.HAP1 complex (PMID:21357693)
• HAP1/stigmoid body interacts with the normal ataxin-3 through Josephin domain (PMID:21386698)
• WT HTT regulates ciliogenesis by interacting through huntingtin-associated protein 1 (HAP1) with pericentriolar material 1 protein (PCM1). (PMID:21985783)
• The results of this study found no association was found between the HAP1 T441M polymorphism and the age at onset of Huntington’s disease . (PMID:22698993)
• The results of this study suggested that HAP1 co-localizes and associates with APP in physiological conditions of mouse and human brain. (PMID:22731248)
• Overexpression of HAP1 reduced in vitro cell growth in breast cancer cell lines. (PMID:23440330)
• The -141 T > G polymorphism, but not the 1349 T > G polymorphism, may have protective effects for lung cancer. (PMID:25081373)
• HAP1 gene expression is related to the radiosensitivity of breast cancer cells and may play an important role in the regulation of cellular radiosensitivity (PMID:25446120)
• data fully support that HAP1 is a GKAP, anchoring specifically to the cGMP-dependent protein kinase isoform Ibeta, and provide further evidence that also PKG spatiotemporal signaling is largely controlled by anchoring proteins (PMID:25653285)
• HAP1 is expressed in endocrine cells of the human gut. (PMID:27737633)
• HAP1 is differentially expressed in the human gastrointestinal tract and is down-regulated in pancreatic adenocarcinoma. (PMID:30560333)
• Acute lymphoblastic leukemia patient leukemic cells with reduced HAP1 levels exhibit resistance to l-asparaginase. (PMID:30819925)
• The adaptor proteins HAP1a and GRIP1 collaborate to activate the kinesin-1 isoform KIF5C. (PMID:31757889)
• Efficient and crucial quality control of HAP1 cell ploidy status. (PMID:33184093)
• Sequential dynein effectors regulate axonal autophagosome motility in a maturation-dependent pathway. (PMID:34014261)
• Differential expression and roles of Huntingtin and Huntingtin-associated protein 1 in the mouse and primate brains. (PMID:36251080)
• Huntingtin-associated protein 1 is a potential tumor suppressor for gastric cancer. (PMID:36509909)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	hap1	ENSDARG00000074508
mus_musculus	Hap1	ENSMUSG00000006930
rattus_norvegicus	Hap1	ENSRNOG00000014819
drosophila_melanogaster	milt	FBGN0262872
caenorhabditis_elegans	trak-1	WBGENE00020838

Paralogs (2): TRAK2 (ENSG00000115993), TRAK1 (ENSG00000182606)

Protein

Protein identifiers

Huntingtin-associated protein 1 — P54257 (reviewed: P54257)

Alternative names: Neuroan 1

All UniProt accessions (4): P54257, H7BZC9, H7C0W9, H7C295

UniProt curated annotations — full annotation on UniProt →

Function. Originally identified as neuronal protein that specifically associates with HTT/huntingtin and the binding is enhanced by an expanded polyglutamine repeat within HTT possibly affecting HAP1 interaction properties. Both HTT and HAP1 are involved in intracellular trafficking and HAP1 is proposed to link HTT to motor proteins and/or transport cargos. Seems to play a role in vesicular transport within neurons and axons such as from early endosomes to late endocytic compartments and to promote neurite outgrowth. The vesicular transport function via association with microtubule-dependent transporters can be attenuated by association with mutant HTT. Involved in the axonal transport of BDNF and its activity-dependent secretion; the function seems to involve HTT, DCTN1 and a complex with SORT1. Involved in APP trafficking and seems to facilitate APP anterograde transport and membrane insertion thereby possibly reducing processing into amyloid beta. Involved in delivery of gamma-aminobutyric acid (GABA(A)) receptors to synapses; the function is dependent on kinesin motor protein KIF5 and is disrupted by HTT with expanded polyglutamine repeat. Involved in regulation of autophagosome motility by promoting efficient retrograde axonal transport. Seems to be involved in regulation of membrane receptor recycling and degradation, and respective signal transduction, including GABA(A) receptors, tyrosine kinase receptors, EGFR, IP3 receptor and androgen receptor. Among others suggested to be involved in control of feeding behavior (involving hypothalamic GABA(A) receptors), cerebellar and brainstem development (involving AHI1 and NTRK1/TrkA), postnatal neurogenesis (involving hypothalamic NTRK2/TrkB), and ITPR1/InsP3R1-mediated Ca(2+) release (involving HTT and possibly the effect of mutant HTT). Via association with DCTN1/dynactin p150-glued and HTT/huntingtin involved in cytoplasmic retention of REST in neurons. May be involved in ciliogenesis. Involved in regulation of exocytosis. Seems to be involved in formation of cytoplasmic inclusion bodies (STBs). In case of anomalous expression of TBP, can sequester a subset of TBP into STBs; sequestration is enhanced by an expanded polyglutamine repeat within TBP. HAP1-containing STBs have been proposed to play a protective role against neurodegeneration in Huntigton disease (HD) and spinocerebellar ataxia 17 (SCA17).

Subunit / interactions. Self-associates. Interacts with HTT/huntingtin; enhanced by an expanded polyglutamine repeat within HTT. Interacts with DCTN1; decreased in presence of HTT with expanded polyglutamine repeat. Interacts with KLC2. Interacts with ITPR1 and APP. Interacts with AR; decreased by an expanded polyglutamine repeat within AR. Interacts with YWHAZ. Interacts with BDNF and SORT1; probably forming a complex involved in proBDNF trafficking, degradation and processing. Interacts with TBP, AHI1, HGS and KALRN. Interacts with KIF5A, KIF5B, KIF5C and GABRB3; indicative for an HAP1:KIF5 complex transporting a GABA(A) receptor as cargo. Interacts with ATXN3; in STBs with ATXN3 poly-Gln region with 27 repeats (normal population) and 79 repeats (spinocerebellar ataxia 3 (SCA3) patients) associating in the same strength. Interacts with NTRK2; HAP1 stabilizes association of NTRK2 with SORT1 preventing NTRK2 degradation. Interacts with CFAP263.

Subcellular location. Cytoplasm. Cell projection. Axon. Presynapse. Cytoskeleton. Dendritic spine. Dendrite. Lysosome. Endoplasmic reticulum. Mitochondrion. Nucleus. Cytoplasmic vesicle. Autophagosome. Early endosome. Growth cone. Neuron projection. Secretory vesicle. Synaptic vesicle.

Tissue specificity. Predominantly expressed in brain. Selectively expressed in neurons.

Miscellaneous. Was not found in huntingtin-containing aggregates in huntigton disease (HD) tissue.

Isoforms (4)

UniProt ID	Names	Canonical?
P54257-1	1	yes
P54257-2	2
P54257-3	3
P54257-4	4

RefSeq proteins (7): NP_001073339, NP_001073340, NP_001354388, NP_001354389, NP_001354390, NP_001354391, NP_817084* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006933	HAP1_N	Domain
IPR051946	Intracell_Traff-Reg	Family

Pfam: PF04849

UniProt features (25 total): sequence variant 11, sequence conflict 4, splice variant 3, region of interest 2, compositionally biased region 2, chain 1, domain 1, coiled-coil region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P54257-F1	64.28	0.27

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 254 (showing top): GOBP_HINDBRAIN_DEVELOPMENT, MODULE_52, GOBP_METENCEPHALON_DEVELOPMENT, GOBP_AXO_DENDRITIC_TRANSPORT, GOBP_REGULATION_OF_CALCIUM_MEDIATED_SIGNALING, YAGI_AML_WITH_INV_16_TRANSLOCATION, GOBP_REGULATION_OF_ERBB_SIGNALING_PATHWAY, GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, GOBP_VESICLE_LOCALIZATION, MODULE_45, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GOBP_PROTEIN_TARGETING, GOBP_REGULATION_OF_EXOCYTOSIS, GOBP_NEUROGENESIS, GOBP_VESICLE_MEDIATED_TRANSPORT

GO Biological Process (25): protein targeting (GO:0006605), exocytosis (GO:0006887), autophagy (GO:0006914), chemical synaptic transmission (GO:0007268), brain development (GO:0007420), anterograde axonal transport (GO:0008089), retrograde axonal transport (GO:0008090), intracellular protein localization (GO:0008104), protein transport (GO:0015031), regulation of exocytosis (GO:0017157), cerebellum development (GO:0021549), hypothalamus cell differentiation (GO:0021979), neurogenesis (GO:0022008), cell projection organization (GO:0030030), obsolete positive regulation of inositol 1,4,5-trisphosphate-sensitive calcium-release channel activity (GO:0031587), positive regulation of synaptic transmission, GABAergic (GO:0032230), positive regulation of neurotrophin production (GO:0032901), positive regulation of epidermal growth factor receptor signaling pathway (GO:0045742), vesicle transport along microtubule (GO:0047496), neurotrophin TRK receptor signaling pathway (GO:0048011), mitochondrion distribution (GO:0048311), positive regulation of neurogenesis (GO:0050769), negative regulation of amyloid-beta formation (GO:1902430), regulation of organelle transport along microtubule (GO:1902513), positive regulation of non-motile cilium assembly (GO:1902857)

GO Molecular Function (5): signaling receptor binding (GO:0005102), myosin binding (GO:0017022), transmembrane transporter binding (GO:0044325), brain-derived neurotrophic factor binding (GO:0048403), protein binding (GO:0005515)

GO Cellular Component (26): nucleolus (GO:0005730), mitochondrion (GO:0005739), lysosome (GO:0005764), early endosome (GO:0005769), autophagosome (GO:0005776), endoplasmic reticulum (GO:0005783), centrosome (GO:0005813), centriole (GO:0005814), cytosol (GO:0005829), cytoskeleton (GO:0005856), synaptic vesicle (GO:0008021), actin cytoskeleton (GO:0015629), inclusion body (GO:0016234), dendrite (GO:0030425), growth cone (GO:0030426), cytoplasmic vesicle (GO:0031410), dendritic spine (GO:0043197), axon cytoplasm (GO:1904115), nucleus (GO:0005634), cytoplasm (GO:0005737), endosome (GO:0005768), axon (GO:0030424), cell projection (GO:0042995), neuron projection (GO:0043005), synapse (GO:0045202), presynapse (GO:0098793)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	4
intracellular membraneless organelle	3
intracellular membrane-bounded organelle	3
establishment of protein localization	2
axonal transport	2
axon cytoplasm	2
cell differentiation	2
protein binding	2
microtubule organizing center	2
cellular anatomical structure	2
intracellular anatomical structure	2
vesicle-mediated transport	1
secretion by cell	1
vesicle fusion to plasma membrane	1
catabolic process	1
transmembrane transport	1
process utilizing autophagic mechanism	1
anterograde trans-synaptic signaling	1
central nervous system development	1
animal organ development	1
head development	1
macromolecule localization	1
transport	1
intracellular protein localization	1
exocytosis	1
regulation of vesicle-mediated transport	1
regulation of secretion by cell	1
metencephalon development	1
anatomical structure development	1
hypothalamus development	1
nervous system development	1
cellular component organization	1
regulation of synaptic transmission, GABAergic	1
positive regulation of synaptic transmission	1
synaptic transmission, GABAergic	1
neurotrophin production	1
regulation of neurotrophin production	1
positive regulation of multicellular organismal process	1
epidermal growth factor receptor signaling pathway	1
regulation of epidermal growth factor receptor signaling pathway	1

Protein interactions and networks

STRING

600 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HAP1	HTT	P42858	997
HAP1	DCTN1	Q14203	979
HAP1	NFYC	Q13952	943
HAP1	REPIN1	Q9BWE0	934
HAP1	KLC2	Q9H0B6	909
HAP1	KLC3	Q6P597	900
HAP1	AHI1	Q8N157	892
HAP1	NFYB	P25208	886
HAP1	KLC4	Q9NSK0	884
HAP1	KLC1	Q07866	875
HAP1	PCM1	Q15154	811
HAP1	BDNF	P23560	765
HAP1	SORT1	Q99523	670
HAP1	NTRK2	Q16620	621
HAP1	F8A2	P23610	583

IntAct

134 interactions, top by confidence:

A	B	Type	Score
HAP1	AHI1	psi-mi:“MI:0915”(physical association)	0.580
AHI1	HAP1	psi-mi:“MI:0915”(physical association)	0.580
HAP1	ZMAT2	psi-mi:“MI:0915”(physical association)	0.560
HAP1	CDK18	psi-mi:“MI:0915”(physical association)	0.560
HAP1	AEN	psi-mi:“MI:0915”(physical association)	0.560
HAP1	FAM50B	psi-mi:“MI:0915”(physical association)	0.560
ZNF490	HAP1	psi-mi:“MI:0915”(physical association)	0.560
HAP1	C2CD6	psi-mi:“MI:0915”(physical association)	0.560
HAP1	C1orf216	psi-mi:“MI:0915”(physical association)	0.560
HAP1	PKN1	psi-mi:“MI:0915”(physical association)	0.560
HAP1	SCNM1	psi-mi:“MI:0915”(physical association)	0.560
HAP1	ZFP1	psi-mi:“MI:0915”(physical association)	0.560
HAP1	PPP1R18	psi-mi:“MI:0915”(physical association)	0.560
HAP1	ZNF575	psi-mi:“MI:0915”(physical association)	0.560
HAP1	CCDC13	psi-mi:“MI:0915”(physical association)	0.560
HAP1	ZNF572	psi-mi:“MI:0915”(physical association)	0.560
HOXB5	HAP1	psi-mi:“MI:0915”(physical association)	0.560
MSGN1	HAP1	psi-mi:“MI:0915”(physical association)	0.560
HAP1	RHPN1	psi-mi:“MI:0915”(physical association)	0.560
HAP1	ZNF835	psi-mi:“MI:0915”(physical association)	0.560
HAP1	ZNF124	psi-mi:“MI:0915”(physical association)	0.560
HAP1	PRPF31	psi-mi:“MI:0915”(physical association)	0.560
HAP1	HDAC4	psi-mi:“MI:0915”(physical association)	0.560
HGS	HAP1	psi-mi:“MI:0915”(physical association)	0.560
HAP1	GABARAPL2	psi-mi:“MI:0915”(physical association)	0.560
HAP1	ZNF648	psi-mi:“MI:0915”(physical association)	0.560
C8orf33	HAP1	psi-mi:“MI:0915”(physical association)	0.550
HMOX2	HAP1	psi-mi:“MI:0915”(physical association)	0.550
RPS10	HAP1	psi-mi:“MI:0915”(physical association)	0.550

BioGRID (145): HSPA1A (Affinity Capture-Western), HSPA1A (Reconstituted Complex), HAP1 (Two-hybrid), DCTN1 (Two-hybrid), HGS (Two-hybrid), HAP1 (Two-hybrid), HAP1 (Affinity Capture-Western), HAP1 (Affinity Capture-Western), HAP1 (Affinity Capture-Western), HAP1 (Affinity Capture-Western), HAP1 (Affinity Capture-Western), HAP1 (Two-hybrid), HAP1 (Two-hybrid), HAP1 (Two-hybrid), HAP1 (Two-hybrid)

ESM2 similar proteins: A0A8I5ZN27, A6X8Z5, E1AZ71, F1N8V3, O35668, O54963, O70318, P20689, P48165, P51954, P54256, P54257, P55917, P62025, P70278, Q01538, Q13029, Q13127, Q14028, Q16799, Q28139, Q28181, Q2M1Z3, Q3SYS4, Q3UH66, Q4KMM3, Q4V8B0, Q5DW34, Q5IS59, Q5TCY1, Q62100, Q63HN8, Q640N3, Q64548, Q6IR42, Q6PCN3, Q7Z6I6, Q811Q2, Q8BYM7, Q8C5W0

Diamond homologs: O35668, O60296, P54256, P54257, Q6PD31, Q9UPV9, Q6GLX3, Q8R2H7, Q960V3

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
HAP1	“up-regulates activity”	KIF5C	binding
HAP1	“up-regulates activity”	AHI1	binding
HAP1	“up-regulates activity”	NEUROD1	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	108
Likely benign	20
Benign	11

Top pathogenic / likely-pathogenic (0)

SpliceAI

1759 predictions. Top by Δscore:

Variant	Effect	Δscore
17:41725150:CATAC:C	acceptor_gain	1.0000
17:41725152:TAC:T	acceptor_gain	1.0000
17:41725152:TACCT:T	acceptor_loss	1.0000
17:41725154:CCTG:C	acceptor_loss	1.0000
17:41725155:CTGG:C	acceptor_loss	1.0000
17:41725156:T:A	acceptor_loss	1.0000
17:41727052:CCT:C	donor_gain	1.0000
17:41727084:T:TA	donor_gain	1.0000
17:41727087:T:TA	donor_gain	1.0000
17:41727832:CCATA:C	acceptor_gain	1.0000
17:41727833:CATA:C	acceptor_gain	1.0000
17:41727833:CATAC:C	acceptor_gain	1.0000
17:41727835:TA:T	acceptor_gain	1.0000
17:41727837:C:CC	acceptor_gain	1.0000
17:41728191:CCCGA:C	donor_gain	1.0000
17:41728199:A:AC	donor_gain	1.0000
17:41728199:AC:A	donor_gain	1.0000
17:41728199:ACCAT:A	donor_gain	1.0000
17:41728200:C:CA	donor_gain	1.0000
17:41728200:CC:C	donor_gain	1.0000
17:41728200:CCAT:C	donor_gain	1.0000
17:41728200:CCATC:C	donor_gain	1.0000
17:41728327:CTCCG:C	acceptor_gain	1.0000
17:41728328:TCCG:T	acceptor_gain	1.0000
17:41728329:CCG:C	acceptor_gain	1.0000
17:41728329:CCGC:C	acceptor_gain	1.0000
17:41728330:CG:C	acceptor_gain	1.0000
17:41728330:CGC:C	acceptor_gain	1.0000
17:41728331:GC:G	acceptor_loss	1.0000
17:41728332:C:CC	acceptor_gain	1.0000

AlphaMissense

3996 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:41731494:A:C	F356L	0.984
17:41731494:A:T	F356L	0.984
17:41731496:A:G	F356L	0.984
17:41731495:A:G	F356S	0.978
17:41728326:C:G	A359P	0.973
17:41732108:A:G	L242P	0.973
17:41728321:G:C	S360R	0.969
17:41728321:G:T	S360R	0.969
17:41728323:T:G	S360R	0.969
17:41728304:A:G	L366P	0.964
17:41731678:A:G	L321P	0.963
17:41731516:A:G	I349T	0.961
17:41728311:C:G	A364P	0.960
17:41731495:A:C	F356C	0.953
17:41732078:A:G	L252P	0.953
17:41732241:C:G	A235P	0.952
17:41734185:A:C	F150L	0.950
17:41734185:A:T	F150L	0.950
17:41734187:A:G	F150L	0.950
17:41734308:G:C	F109L	0.948
17:41734308:G:T	F109L	0.948
17:41734310:A:G	F109L	0.948
17:41732261:A:G	L228P	0.942
17:41731648:A:G	L331P	0.940
17:41728241:A:G	L387P	0.937
17:41732075:A:G	L253P	0.937
17:41732087:C:G	R249P	0.934
17:41731669:A:G	L324P	0.932
17:41728292:A:G	L370P	0.929
17:41731516:A:C	I349S	0.927

dbSNP variants (sampled 300 via entrez): RS1000029559 (17:41733673 G>A), RS1001046677 (17:41722097 C>G,T), RS1001425520 (17:41722292 C>T), RS1001802930 (17:41717614 C>A,G,T), RS1002089912 (17:41724520 G>C), RS1002263912 (17:41734778 G>A), RS1002494864 (17:41720496 A>G), RS1002697666 (17:41725684 G>C), RS1003130371 (17:41725428 G>C,T), RS1003201284 (17:41730345 A>C,G), RS1003299117 (17:41735737 G>A), RS1003941065 (17:41735573 G>A), RS1004495047 (17:41720477 G>A), RS1004962300 (17:41724218 T>C,G), RS1004994892 (17:41724040 T>C)

Disease associations

OMIM: gene MIM:600947 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Estradiol	affects cotreatment, decreases expression, increases expression	2
Cadmium Chloride	increases expression	2
aristolochic acid I	increases expression	1
OTX015	increases expression	1
mivebresib	increases expression	1
ethyl-p-hydroxybenzoate	decreases expression	1
sodium arsenite	affects cotreatment, increases abundance, increases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
2-palmitoylglycerol	increases expression	1
abrine	increases expression	1
jinfukang	affects cotreatment, increases expression	1
(+)-JQ1 compound	increases expression	1
Fulvestrant	increases methylation	1
Acetaminophen	increases expression	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Atrazine	increases expression	1
Benzo(a)pyrene	increases methylation	1
Cisplatin	affects cotreatment, increases expression	1
Doxorubicin	increases expression	1
Folic Acid	increases expression	1
Manganese	affects cotreatment, increases abundance, increases expression	1
Smoke	decreases expression	1
Thiram	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Urethane	increases expression	1
Aflatoxin B1	increases expression	1
Okadaic Acid	increases expression	1
Acrylamide	increases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_E1YU	HAP1 HAP1 (-) 1	Cancer cell line	Male
CVCL_E1YV	HAP1 HAP1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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