ZNHIT1

Summary

ZNHIT1 (zinc finger HIT-type containing 1, HGNC:21688) is a protein-coding gene on chromosome 7q22.1, encoding Zinc finger HIT domain-containing protein 1 (O43257). Plays a role in chromatin remodeling by promoting the incorporation of histone variant H2AZ1/H2A.Z into the genome to regulate gene expression. It is a selective cancer dependency (DepMap: 22.6% of cell lines).

Enables histone binding activity. Involved in muscle cell differentiation and positive regulation of DNA damage response, signal transduction by p53 class mediator. Located in nucleoplasm.

Source: NCBI Gene 10467 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 28 total
• Cancer dependency (DepMap): dependent in 22.6% of screened cell lines
• MANE Select transcript: NM_006349

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21688
Approved symbol	ZNHIT1
Name	zinc finger HIT-type containing 1
Location	7q22.1
Locus type	gene with protein product
Status	Approved
Aliases	CG1I, H_DJ0747G18.14, p18(Hamlet)
Ensembl gene	ENSG00000106400
Ensembl biotype	protein_coding
OMIM	618617
Entrez	10467

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 3 protein_coding, 2 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000305105, ENST00000461205, ENST00000485387, ENST00000492315, ENST00000890490, ENST00000956465

RefSeq mRNA: 1 — MANE Select: NM_006349 NM_006349

CCDS: CCDS5716

Canonical transcript exons

ENST00000305105 — 5 exons

Exon	Start	End
ENSE00001178270	101218165	101218217
ENSE00003529957	101223477	101223556
ENSE00003657799	101223673	101223842
ENSE00003668985	101223937	101224190
ENSE00003675862	101222604	101222774

Expression profiles

Bgee: expression breadth ubiquitous, 291 present calls, max score 98.75.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 109.5045 / max 643.6660, expressed in 1827 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
80185	107.4224	1827
80184	2.0821	1131

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	98.75	gold quality
mucosa of transverse colon	UBERON:0004991	98.23	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	98.13	gold quality
apex of heart	UBERON:0002098	97.52	gold quality
body of stomach	UBERON:0001161	97.42	gold quality
right lobe of thyroid gland	UBERON:0001119	97.31	gold quality
right adrenal gland	UBERON:0001233	97.31	gold quality
left adrenal gland cortex	UBERON:0035825	97.25	gold quality
right adrenal gland cortex	UBERON:0035827	97.21	gold quality
right uterine tube	UBERON:0001302	97.20	gold quality
metanephros cortex	UBERON:0010533	97.18	gold quality
left adrenal gland	UBERON:0001234	97.17	gold quality
left lobe of thyroid gland	UBERON:0001120	97.14	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	97.10	gold quality
left coronary artery	UBERON:0001626	97.03	gold quality
liver	UBERON:0002107	97.01	gold quality
transverse colon	UBERON:0001157	97.00	gold quality
omental fat pad	UBERON:0010414	97.00	gold quality
peritoneum	UBERON:0002358	96.97	gold quality
caudate nucleus	UBERON:0001873	96.94	gold quality
adenohypophysis	UBERON:0002196	96.94	gold quality
spinal cord	UBERON:0002240	96.87	gold quality
nucleus accumbens	UBERON:0001882	96.86	gold quality
lower esophagus	UBERON:0013473	96.85	gold quality
lower esophagus muscularis layer	UBERON:0035833	96.85	gold quality
endocervix	UBERON:0000458	96.84	gold quality
amygdala	UBERON:0001876	96.78	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	96.77	gold quality
muscle layer of sigmoid colon	UBERON:0035805	96.74	gold quality
right atrium auricular region	UBERON:0006631	96.73	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-7606	no	918.27
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
MYOG	Activation

miRNA regulators (miRDB)

16 targeting ZNHIT1, 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-6888-3P	99.97	65.95	1170
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-221-5P	99.86	65.45	1052
HSA-MIR-8073	99.86	65.21	1118
HSA-MIR-4743-3P	99.62	68.12	2095
HSA-MIR-330-5P	98.73	67.63	1788
HSA-MIR-6830-3P	98.62	68.07	1760
HSA-MIR-3188	98.58	65.60	878
HSA-MIR-326	98.25	66.44	1565
HSA-MIR-1262	98.17	66.52	757
HSA-MIR-4701-3P	98.17	66.25	788
HSA-MIR-6736-5P	98.17	66.43	760
HSA-MIR-6801-3P	98.04	64.64	805
HSA-MIR-6810-3P	97.96	64.57	1023
HSA-MIR-7111-3P	97.80	66.75	1467

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 22.6% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 5)

• p18(Hamlet) is a new cell-fate regulator that links the p38 MAPK and p53 pathways and contributes to the establishment of p53-regulated stress responses. (PMID:17380123)
• Study reports that p18(Hamlet) can also mediate the cell cycle arrest induced in response to gamma-irradiation, by participating in the p53-dependent upregulation of the cell cycle inhibitor p21(Cip1) (CDKN1A). (PMID:17700068)
• Gene Co-expression Analysis of the Human Substantia Nigra Identifies ZNHIT1 as an SNCA Co-expressed Gene that Protects Against alpha-Synuclein-Induced Impairments in Neurite Growth and Mitochondrial Dysfunction in SH-SY5Y Cells. (PMID:35175558)
• Znhit1 and HIF-2alpha are correlated with cancer stem cell markers in breast cancer patients. (PMID:35978075)
• A combined proteomics and bioinformatics analysis of ZNHIT1-interacting proteins reveals a significant enrichment in proteins associated with mitochondrial function. (PMID:37178741)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	znhit1	ENSDARG00000054574
mus_musculus	Znhit1	ENSMUSG00000059518
rattus_norvegicus	Znhit1	ENSRNOG00000001418
drosophila_melanogaster	CG31917	FBGN0031668
caenorhabditis_elegans		WBGENE00016992

Protein

Protein identifiers

Zinc finger HIT domain-containing protein 1 — O43257 (reviewed: O43257)

Alternative names: Cyclin-G1-binding protein 1, Zinc finger protein subfamily 4A member 1, p18 Hamlet

All UniProt accessions (1): O43257

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in chromatin remodeling by promoting the incorporation of histone variant H2AZ1/H2A.Z into the genome to regulate gene expression. Promotes SRCAP complex-mediated deposition of histone variant H2AZ1 to lymphoid fate regulator genes, enhancing lymphoid lineage commitment. Recruited to the promoter of the transcriptional activator MYOG at the early stages of muscle differentiation where it mediates binding of histone H2AZ1 to chromatin and induces muscle-specific gene expression. Maintains hematopoietic stem cell (HSC) quiescence by determining the chromatin accessibility at distal enhancers of HSC quiescence genes such as PTEN, FSTL1 and KLF4, enhancing deposition of H2AZ1 to promote their sustained transcription and restricting PI3K-AKT signaling inhibition. Plays a role in intestinal stem cell maintenance by promoting H2AZ1 deposition at the transcription start sites of genes involved in intestinal stem cell fate determination including LGR5, TGFB1 and TGFBR2, thereby contributing to gene transcription. Promotes phosphorylation of the H2AZ1 chaperone VPS72/YL1 which enhances the interaction between HZAZ1 and VPS72. Regulates the entry of male germ cells into meiosis by controlling histone H2AZ1 deposition which facilitates the expression of meiotic genes such as MEIOSIN, leading to the initiation of meiosis. Required for postnatal heart function through its role in maintenance of cardiac Ca(2+) homeostasis by modulating the expression of Ca(2+)-regulating proteins CASQ1 and ATP2A2/SERCA2A via deposition of histone H2AZ1 at their promoters. During embryonic heart development, required for mitochondrial maturation and oxidative metabolism by functioning through H2AZ1 deposition to activate transcription of metabolic genes and is also required to maintain the stability of the respiratory complex. In neural cells, increases deposition of the H2AZ1 histone variant and promotes neurite growth. Plays a role in TP53/p53-mediated apoptosis induction by stimulating the transcriptional activation of several proapoptotic p53 target genes such as PMAIP1/NOXA and BBC3/PUMA. Mediates cell cycle arrest induced in response to gamma-irradiation by enhancing recruitment of TP53/p53 to the promoter of the cell cycle inhibitor CDKN1A, leading to its transcriptional activation. Recruited to the promoter of cyclin-dependent kinase CDK6 and inhibits its transcription, possibly by decreasing the acetylation level of histone H4, leading to cell cycle arrest at the G1 phase. Plays a role in lens fiber cell differentiation by regulating the expression of cell cycle regulator CDKN1A/p21Cip1. Binds to transcriptional repressor NR1D2 and relieves it of its inhibitory effect on the transcription of apolipoprotein APOC3 without affecting its DNA-binding activity.

Subunit / interactions. Component of the chromatin-remodeling SRCAP complex composed of at least SRCAP, DMAP1, RUVBL1, RUVBL2, ACTL6A, YEATS4, ACTR6 and ZNHIT1. Interacts with MAPK11 and MAPK14. Interacts with NR1D1 and NR2D2. Interacts (via HIT-type zinc finger) with the RUVBL1/RUVBL2 complex in the presence of ADP. Interacts with histone deacetylase HDAC1. Interacts with histone H2AZ1; the interaction results in recruitment of H2AZ1 to the MYOG promoter region. Interacts with PCID2; the interaction results in inhibition of SRCAP complex activity, preventing the deposition of histone variant H2AZ1 to lymphoid fate regulator genes and restricting lymphoid lineage commitment.

Subcellular location. Nucleus.

Tissue specificity. Expressed abundantly in liver, but weakly in skeletal muscle, ovary and small intestine.

Post-translational modifications. Phosphorylated on Thr by MAPK11 or MAPK14. Phosphorylation is required for MYOG induction, for deposition of histone H2AZ1 at the MYOG promoter and for SRCAP complex integrity.

Induction. Induced by DNA damage.

Similarity. Belongs to the ZNHIT1 family.

RefSeq proteins (1): NP_006340* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007529	Znf_HIT	Domain
IPR039723	Vps71/ZNHIT1	Family

Pfam: PF04438

UniProt features (19 total): binding site 8, mutagenesis site 2, region of interest 2, chain 1, zinc finger region 1, modified residue 1, sequence variant 1, coiled-coil region 1, short sequence motif 1, compositionally biased region 1

Structure

Experimental structures (PDB)

8 structures.

PDB	Method	Resolution (Å)
8X15	ELECTRON MICROSCOPY	3.2
8X19	ELECTRON MICROSCOPY	3.2
8X1C	ELECTRON MICROSCOPY	3.2
9CA7	ELECTRON MICROSCOPY	3.35
9CA9	ELECTRON MICROSCOPY	3.56
9CA8	ELECTRON MICROSCOPY	3.92
9CAB	ELECTRON MICROSCOPY	3.94
9CAA	ELECTRON MICROSCOPY	4.04

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O43257-F1	73.92	0.23

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): 131; 136; 140; 144; 149; 117; 120; 128

Post-translational modifications (1): 103

Mutagenesis-validated functional residues (2):

Position	Phenotype
103	impairs the p38 mapk-mediated phosphorylation of znhit1.
124	no change in the in vitro mapk14/mapk11-induced phosphorylation level of znhit1.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 225 (showing top): GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_HEMATOPOIETIC_PROGENITOR_CELL_DIFFERENTIATION, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, GOBP_POSITIVE_REGULATION_OF_DNA_DAMAGE_RESPONSE_SIGNAL_TRANSDUCTION_BY_P53_CLASS_MEDIATOR, TGCGCANK_UNKNOWN, GOBP_CIRCULATORY_SYSTEM_PROCESS, MODULE_151, ENK_UV_RESPONSE_KERATINOCYTE_UP, GOBP_POSITIVE_REGULATION_OF_DNA_TEMPLATED_TRANSCRIPTION_INITIATION, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, DACOSTA_UV_RESPONSE_VIA_ERCC3_UP, GOBP_REGULATION_OF_DNA_DAMAGE_RESPONSE_SIGNAL_TRANSDUCTION_BY_P53_CLASS_MEDIATOR, GOBP_POSITIVE_REGULATION_OF_SIGNAL_TRANSDUCTION_BY_P53_CLASS_MEDIATOR, GOBP_LEUKOCYTE_PROLIFERATION

GO Biological Process (15): negative regulation of transcription by RNA polymerase II (GO:0000122), heart process (GO:0003015), chromatin remodeling (GO:0006338), regulation of DNA-templated transcription (GO:0006355), intestinal stem cell homeostasis (GO:0036335), regulation of T cell proliferation (GO:0042129), muscle cell differentiation (GO:0042692), positive regulation of DNA damage response, signal transduction by p53 class mediator (GO:0043517), transcription initiation-coupled chromatin remodeling (GO:0045815), calcium ion homeostasis (GO:0055074), positive regulation of transcription initiation by RNA polymerase II (GO:0060261), hematopoietic stem cell homeostasis (GO:0061484), negative regulation of G0 to G1 transition (GO:0070317), positive regulation of lymphoid progenitor cell differentiation (GO:1905458), chromatin organization (GO:0006325)

GO Molecular Function (7): zinc ion binding (GO:0008270), nucleosome binding (GO:0031491), histone binding (GO:0042393), histone deacetylase binding (GO:0042826), chromatin binding (GO:0003682), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (4): nucleosome (GO:0000786), Swr1 complex (GO:0000812), nucleus (GO:0005634), nucleoplasm (GO:0005654)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
homeostasis of number of cells	2
transcription initiation at RNA polymerase II promoter	2
binding	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
circulatory system process	1
chromatin organization	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
T cell proliferation	1
regulation of lymphocyte proliferation	1
regulation of T cell activation	1
cell differentiation	1
muscle structure development	1
DNA damage response, signal transduction by p53 class mediator	1
regulation of DNA damage response, signal transduction by p53 class mediator	1
positive regulation of signal transduction by p53 class mediator	1
positive regulation of gene expression, epigenetic	1
monoatomic cation homeostasis	1
inorganic ion homeostasis	1
positive regulation of transcription by RNA polymerase II	1
regulation of transcription initiation by RNA polymerase II	1
positive regulation of DNA-templated transcription initiation	1
negative regulation of cell cycle process	1
G0 to G1 transition	1
regulation of G0 to G1 transition	1
lymphoid progenitor cell differentiation	1
positive regulation of hematopoietic progenitor cell differentiation	1
regulation of lymphoid progenitor cell differentiation	1
cellular component organization	1
transition metal ion binding	1
chromatin binding	1
protein-containing complex binding	1
protein binding	1
enzyme binding	1
cation binding	1
chromatin	1
protein-DNA complex	1

Protein interactions and networks

STRING

1356 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZNHIT1	VPS72	Q15906	852
ZNHIT1	H2AZ1	P0C0S5	784
ZNHIT1	SRCAP	Q6ZRS2	761
ZNHIT1	RUVBL1	P82276	722
ZNHIT1	ZNHIT6	Q9NWK9	694
ZNHIT1	INO80B	Q9C086	673
ZNHIT1	ACTL6A	O96019	610
ZNHIT1	H1-1	Q02539	586
ZNHIT1	ZNHIT3	Q15649	570
ZNHIT1	PCID2	Q5JVF3	570
ZNHIT1	MRGBP	Q9NV56	560
ZNHIT1	RUVBL2	Q9Y230	545
ZNHIT1	H2AZ2	Q71UI9	538
ZNHIT1	CXCL11	O14625	537
ZNHIT1	SMARCD3	Q6STE5	535

IntAct

139 interactions, top by confidence:

A	B	Type	Score
RUVBL1	ZNHIT1	psi-mi:“MI:0914”(association)	0.860
ACTR6	ZNHIT1	psi-mi:“MI:0914”(association)	0.820
ACTR6	ZNHIT1	psi-mi:“MI:0915”(physical association)	0.820
RUVBL2	ZNHIT1	psi-mi:“MI:0914”(association)	0.810
YEATS4	ZNHIT1	psi-mi:“MI:0914”(association)	0.790
ZNHIT1	YEATS4	psi-mi:“MI:0914”(association)	0.790
H2AZ1	ZNHIT1	psi-mi:“MI:0914”(association)	0.770
ZNHIT1	H2AZ1	psi-mi:“MI:0915”(physical association)	0.770
H2AZ1	ZNHIT1	psi-mi:“MI:0915”(physical association)	0.770
ZNHIT1	H2AZ1	psi-mi:“MI:0914”(association)	0.770
MAPK14	ZNHIT1	psi-mi:“MI:0915”(physical association)	0.720
ZNHIT1	MAPK14	psi-mi:“MI:0915”(physical association)	0.720
ZNHIT1	MAPK14	psi-mi:“MI:0217”(phosphorylation reaction)	0.720
ZNHIT1	ACTL6A	psi-mi:“MI:0914”(association)	0.720
ACTL6A	ZNHIT1	psi-mi:“MI:0914”(association)	0.720
VPS72	ZNHIT1	psi-mi:“MI:0914”(association)	0.690
H2BC1	PPM1G	psi-mi:“MI:0914”(association)	0.640
P4HA3	FAM171A2	psi-mi:“MI:0914”(association)	0.640
RUVBL2	POLR3A	psi-mi:“MI:0914”(association)	0.640
RUVBL1	POLR3A	psi-mi:“MI:0914”(association)	0.640

BioGRID (93): ZNHIT1 (Two-hybrid), KRTAP10-7 (Two-hybrid), ZNHIT1 (Affinity Capture-MS), ZNHIT1 (Affinity Capture-MS), ZNHIT1 (Affinity Capture-MS), ZNHIT1 (Two-hybrid), ZNHIT1 (Two-hybrid), ZNHIT1 (Two-hybrid), ZNHIT1 (Affinity Capture-MS), ZNHIT1 (Affinity Capture-MS), ZNHIT1 (Affinity Capture-MS), ZNHIT1 (Affinity Capture-MS), ZNHIT1 (Affinity Capture-MS), ZNHIT1 (Affinity Capture-MS), ZNHIT1 (Affinity Capture-MS)

ESM2 similar proteins: A0A4X1TB62, O43257, O60941, O70524, O70585, O95983, P13413, P13984, P27089, P84060, Q01750, Q0P5J8, Q24JY4, Q2KJ58, Q2T9L9, Q4V8D7, Q4VA36, Q5BK68, Q5R660, Q5R7S4, Q5R7U7, Q5RB75, Q5RJG1, Q5T6S3, Q5VSL9, Q66H91, Q68FF6, Q6DDJ3, Q6DJB3, Q7T0P6, Q86UT8, Q8C079, Q8C790, Q8C9H6, Q8CBY8, Q8IVD9, Q8R1N4, Q8R331, Q8TBN0, Q8VHE0

Diamond homologs: O43257, O59669, Q24JY4, Q4U9I8, Q54NW0, Q8R331, Q9FHW2, A4HK17, A5E240, A7AT07, B0EKR0, C0S6S4, C1G4S9, C1GWM2, C4M6U3, P93042, Q0JLS6, Q2QMH2, Q2R224, Q4DHA1, Q4N280, Q4PEQ0, Q6CJ97, Q8ILT5, Q9FKE9, Q9SSN0, Q9UTE0, Q03433

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
MAPK14	up-regulates	ZNHIT1	phosphorylation
ZNHIT1	unknown	H2AZ1
ZNHIT1	“up-regulates quantity by expression”	MYOG	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 63 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
HATs acetylate histones	8	15.5×	2e-05
Oxidative Stress Induced Senescence	6	13.3×	9e-04
Amyloid fiber formation	5	12.6×	2e-03
Signaling by Interleukins	5	7.8×	7e-03

GO biological processes:

GO term	Partners	Fold	FDR
regulation of double-strand break repair	6	67.0×	1e-07
positive regulation of double-strand break repair via homologous recombination	6	44.2×	1e-06
positive regulation of DNA repair	6	41.4×	1e-06
regulation of cell cycle	8	11.5×	3e-05
regulation of apoptotic process	7	11.2×	1e-04
chromatin remodeling	7	9.8×	3e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	22
Likely benign	0
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

614 predictions. Top by Δscore:

Variant	Effect	Δscore
7:101222602:A:AG	acceptor_gain	1.0000
7:101222603:G:GA	acceptor_gain	1.0000
7:101222603:GTT:G	acceptor_gain	1.0000
7:101222603:GTTC:G	acceptor_gain	1.0000
7:101222737:C:T	donor_gain	1.0000
7:101222771:ACTGG:A	donor_loss	1.0000
7:101222775:G:GG	donor_gain	1.0000
7:101222775:GTGA:G	donor_loss	1.0000
7:101222776:T:G	donor_loss	1.0000
7:101222793:G:GT	donor_gain	1.0000
7:101223667:CTGCA:C	acceptor_loss	1.0000
7:101223668:TGCAG:T	acceptor_loss	1.0000
7:101223669:GCAGA:G	acceptor_loss	1.0000
7:101223670:CA:C	acceptor_loss	1.0000
7:101223671:A:AG	acceptor_gain	1.0000
7:101223672:G:GT	acceptor_gain	1.0000
7:101223672:GA:G	acceptor_gain	1.0000
7:101223672:GAA:G	acceptor_gain	1.0000
7:101223672:GAAC:G	acceptor_gain	1.0000
7:101223672:GAACT:G	acceptor_gain	1.0000
7:101223932:TGCA:T	acceptor_loss	1.0000
7:101223934:CA:C	acceptor_loss	1.0000
7:101223935:A:AC	acceptor_loss	1.0000
7:101222602:AGTTC:A	acceptor_gain	0.9900
7:101222603:GT:G	acceptor_gain	0.9900
7:101222603:GTTCG:G	acceptor_gain	0.9900
7:101222705:G:GT	donor_gain	0.9900
7:101222790:G:GT	donor_gain	0.9900
7:101223439:G:A	acceptor_gain	0.9900
7:101223444:A:G	acceptor_gain	0.9900

AlphaMissense

990 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:101222698:C:A	N39K	0.999
7:101222698:C:G	N39K	0.999
7:101223518:C:A	R79S	0.999
7:101223521:T:C	F80L	0.999
7:101223523:C:A	F80L	0.999
7:101223523:C:G	F80L	0.999
7:101223529:A:C	K82N	0.999
7:101223529:A:T	K82N	0.999
7:101223748:T:C	C117R	0.999
7:101223749:G:A	C117Y	0.999
7:101223761:G:A	G121D	0.999
7:101223781:T:C	C128R	0.999
7:101223791:G:A	C131Y	0.999
7:101223817:T:C	C140R	0.999
7:101223842:G:T	R148M	0.999
7:101223946:G:C	K151N	0.999
7:101223946:G:T	K151N	0.999
7:101222676:T:C	L32P	0.998
7:101223512:A:G	K77E	0.998
7:101223514:A:C	K77N	0.998
7:101223514:A:T	K77N	0.998
7:101223522:T:C	F80S	0.998
7:101223528:A:T	K82I	0.998
7:101223534:T:C	F84S	0.998
7:101223543:T:C	L87P	0.998
7:101223750:T:G	C117W	0.998
7:101223757:T:C	C120R	0.998
7:101223758:G:A	C120Y	0.998
7:101223782:G:A	C128Y	0.998
7:101223790:T:C	C131R	0.998

dbSNP variants (sampled 300 via entrez): RS1000262219 (7:101220088 T>A,C), RS1000289370 (7:101220133 T>C), RS1001458575 (7:101217056 G>A,C), RS1001843506 (7:101217963 G>A), RS1003250709 (7:101216942 G>A,T), RS1003453723 (7:101219473 C>G), RS1003484664 (7:101219695 G>A,C), RS1003678017 (7:101220832 A>G), RS1003730400 (7:101220550 C>T), RS1004000148 (7:101218013 AGT>A), RS1004831640 (7:101222175 A>G), RS1005128502 (7:101220826 G>A), RS1005162969 (7:101221278 G>A), RS1005219949 (7:101216631 C>T), RS1005465111 (7:101222197 A>T)

Disease associations

OMIM: gene MIM:618617 | 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

13 total (human), top 13 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases methylation, affects expression, increases expression	3
Benzo(a)pyrene	decreases expression, increases methylation	2
triphenyl phosphate	affects expression	1
sodium arsenite	increases abundance, increases expression	1
di-n-butylphosphoric acid	affects expression	1
K 7174	decreases expression	1
Acetaminophen	decreases expression	1
Arsenic	increases abundance, increases expression	1
Cannabidiol	increases expression	1
Diuron	decreases expression	1
Cyclosporine	decreases expression	1
Cadmium Chloride	increases expression	1
tert-Butylhydroperoxide	decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B3LN	Abcam HEK293T ZNHIT1 KO	Transformed cell line	Female

Clinical trials (associated diseases)

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