ZNF746

Summary

ZNF746 (zinc finger protein 746, HGNC:21948) is a protein-coding gene on chromosome 7q36.1, encoding Zinc finger protein 746 (Q6NUN9). Transcription repressor that specifically binds to the 5’-TATTTT[T/G]-3’ consensus sequence on promoters and repress transcription of PGC-1-alpha (PPARGC1A), thereby playing a role in regulation of neuron death.

Enables DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Involved in protein complex oligomerization and regulation of transcription by RNA polymerase II. Located in cytosol and nucleoplasm.

Source: NCBI Gene 155061 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 87 total
• MANE Select transcript: NM_001394198

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21948
Approved symbol	ZNF746
Name	zinc finger protein 746
Location	7q36.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ31413, PARIS
Ensembl gene	ENSG00000181220
Ensembl biotype	protein_coding
OMIM	613914
Entrez	155061

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 6 protein_coding, 1 retained_intron

ENST00000340622, ENST00000458143, ENST00000461958, ENST00000471735, ENST00000644635, ENST00000685153, ENST00000922194

RefSeq mRNA: 4 — MANE Select: NM_001394198 NM_001163474, NM_001363517, NM_001394198, NM_152557

CCDS: CCDS55180, CCDS5897, CCDS87562, CCDS94227

Canonical transcript exons

ENST00000458143 — 7 exons

Exon	Start	End
ENSE00002320908	149472794	149475483
ENSE00002368125	149477564	149477755
ENSE00002452191	149494204	149494503
ENSE00002483668	149492859	149492972
ENSE00003630259	149476922	149477047
ENSE00003818950	149493989	149494115
ENSE00003843444	149497513	149497809

Expression profiles

Bgee: expression breadth ubiquitous, 233 present calls, max score 91.76.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.0490 / max 239.8198, expressed in 1802 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
86734	6.7046	1766
86735	4.3444	1651

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
blood	UBERON:0000178	91.76	gold quality
granulocyte	CL:0000094	88.05	gold quality
ileal mucosa	UBERON:0000331	85.23	gold quality
spleen	UBERON:0002106	84.89	gold quality
leukocyte	CL:0000738	83.40	gold quality
monocyte	CL:0000576	83.05	gold quality
bone marrow cell	CL:0002092	82.93	gold quality
cortical plate	UBERON:0005343	82.81	gold quality
left testis	UBERON:0004533	82.76	gold quality
stromal cell of endometrium	CL:0002255	82.42	gold quality
testis	UBERON:0000473	82.42	gold quality
right testis	UBERON:0004534	82.41	gold quality
sural nerve	UBERON:0015488	82.25	gold quality
secondary oocyte	CL:0000655	82.17	gold quality
pancreatic ductal cell	CL:0002079	81.82	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	81.80	gold quality
right hemisphere of cerebellum	UBERON:0014890	81.76	gold quality
cerebellar hemisphere	UBERON:0002245	81.62	gold quality
cerebellar cortex	UBERON:0002129	81.59	gold quality
mucosa of stomach	UBERON:0001199	81.49	gold quality
bone marrow	UBERON:0002371	81.46	gold quality
cerebellum	UBERON:0002037	81.26	gold quality
placenta	UBERON:0001987	81.19	gold quality
apex of heart	UBERON:0002098	81.14	gold quality
pituitary gland	UBERON:0000007	81.05	gold quality
left uterine tube	UBERON:0001303	81.02	gold quality
right lung	UBERON:0002167	80.96	gold quality
lower esophagus muscularis layer	UBERON:0035833	80.96	gold quality
lower esophagus	UBERON:0013473	80.93	gold quality
adenohypophysis	UBERON:0002196	80.89	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.91

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

3 targets.

Target	Regulation
INS
PCK1	Activation
PPARGC1A	Repression

JASPAR motifs

Motif	Name	Family
MA2570.1	ZNF746	More than 3 adjacent zinc fingers

JASPAR matrix evidence (PMIDs): PMID:39605320

Upstream regulators (CollecTRI, top): STAT1

miRNA regulators (miRDB)

38 targeting ZNF746, 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-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-4648	99.91	67.00	710
HSA-MIR-370-5P	99.78	66.81	706
HSA-MIR-6762-3P	99.66	66.94	1188
HSA-MIR-3136-3P	99.57	66.59	781
HSA-MIR-7155-3P	99.57	66.48	794
HSA-MIR-7159-5P	99.53	72.12	2472
HSA-MIR-3123	99.47	67.15	2693
HSA-MIR-6722-3P	99.45	67.62	1919
HSA-MIR-16-2-3P	99.29	70.60	1954
HSA-MIR-195-3P	99.29	70.61	1954
HSA-MIR-329-5P	99.27	68.11	1597
HSA-MIR-140-3P	99.04	67.69	1324
HSA-MIR-670-3P	99.03	68.88	2404
HSA-MIR-1909-3P	99.03	66.56	1662
HSA-MIR-6814-5P	99.03	66.68	1273
HSA-MIR-603	98.58	68.28	1603
HSA-MIR-676-5P	98.49	68.87	1492
HSA-MIR-147A	98.33	66.40	795
HSA-MIR-3074-3P	97.83	67.26	922
HSA-MIR-6893-3P	97.79	64.91	1238

Literature-anchored findings (GeneRIF, showing 14)

• PARIS(ZNF746) is a KRAB and zinc finger protein that accumulates in models of parkin inactivation and in human PD brain. (PMID:21376232)
• these findings suggest that inhibition of ZNF746 suppresses the invasion and epithelial to mesenchymal transition molecules in H460 NSCLC cells and ZNF746 may be an important target molecule in lung tumorigenesis. (PMID:24145959)
• PARIS overexpression leads to reduced mitochondrial number and structural abnormalities (PMID:26324925)
• Taken together, these results suggest that PARIS and PIASy modulate PGC-1a gene transcription through distinct molecular mechanisms. (PMID:27086851)
• the findings suggest that ZNF746 promotes colorectal cancer progression via c-Myc stability mediated by glycogen synthase kinase 3beta and F-box/WD repeat-containing protein 7. (PMID:29628506)
• We show that parkin is inactivated leading to the accumulation of parkin interacting substrate protein (PARIS) (zinc finger protein 746) (ZNF746) in 3 models of Parkinson’s disease (PMID:31237944)
• PARIS induced defects in mitochondrial biogenesis drive dopamine neuron loss under conditions of parkin or PINK1 deficiency. (PMID:32138754)
• RNF4-mediated SUMO-targeted ubiquitination relieves PARIS/ZNF746-mediated transcriptional repression. (PMID:32197837)
• PARIS-DJ-1 Interaction Regulates Mitochondrial Functions in Cardiomyocytes, Which Is Critically Important in Cardiac Hypertrophy. (PMID:33077496)
• Genetic Analysis of ZNF Protein Family Members for Early-Onset Parkinson’s Disease in Chinese Population. (PMID:33723766)
• ZNF746/PARIS promotes the occurrence of hepatocellular carcinoma. (PMID:34062393)
• ZNF746 promotes M2 macrophage polarisation and favours tumour progression in breast cancer via the Jagged1/Notch pathway. (PMID:37730102)
• PARIS undergoes liquid-liquid phase separation and poly(ADP-ribose)-mediated solidification. (PMID:37870275)
• Unveiling the regulatory of miR-101-3p on ZNF746 in a Parkinson’s disease cell model: Implications for therapeutic targeting. (PMID:38103579)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Zfp746	ENSMUSG00000057691
rattus_norvegicus	Zfp746	ENSRNOG00000007064

Paralogs (51): WIZ (ENSG00000011451), ZNF416 (ENSG00000083817), MYNN (ENSG00000085274), PRDM4 (ENSG00000110851), PRDM2 (ENSG00000116731), ZBTB17 (ENSG00000116809), ZNF644 (ENSG00000122482), GZF1 (ENSG00000125812), ZNF426 (ENSG00000130818), ZNF287 (ENSG00000141040), ZNF697 (ENSG00000143067), ZNF687 (ENSG00000143373), ZNF214 (ENSG00000149050), ZNF547 (ENSG00000152433), ZNF776 (ENSG00000152443), ZNF230 (ENSG00000159882), ZNF222 (ENSG00000159885), ZNF233 (ENSG00000159915), ZNF333 (ENSG00000160961), ZNF319 (ENSG00000166188), ZNF592 (ENSG00000166716), ZNF646 (ENSG00000167395), ZNF507 (ENSG00000168813), ZNF768 (ENSG00000169957), ZNF417 (ENSG00000173480), ZNF408 (ENSG00000175213), ZBTB41 (ENSG00000177888), ZNF223 (ENSG00000178386), ZNF852 (ENSG00000178917), ZNF784 (ENSG00000179922), ZNF572 (ENSG00000180938), ZNF707 (ENSG00000181135), ZNF467 (ENSG00000181444), ZNF530 (ENSG00000183647), ZNF17 (ENSG00000186272), ZNF527 (ENSG00000189164), ZKSCAN7 (ENSG00000196345), ZNF34 (ENSG00000196378), ZNF774 (ENSG00000196391), ZNF777 (ENSG00000196453)

Protein

Protein identifiers

Zinc finger protein 746 — Q6NUN9 (reviewed: Q6NUN9)

Alternative names: Parkin-interacting substrate

All UniProt accessions (4): Q6NUN9, A0A2R8YDQ5, A0A8J9FQ52, C9JNZ9

UniProt curated annotations — full annotation on UniProt →

Function. Transcription repressor that specifically binds to the 5’-TATTTT[T/G]-3’ consensus sequence on promoters and repress transcription of PGC-1-alpha (PPARGC1A), thereby playing a role in regulation of neuron death.

Subunit / interactions. Homooligomer, heterooligomer with ZNF746. Interacts (via C2H2-type zinc fingers) with PRKN. Interacts with TRIM28.

Subcellular location. Cytoplasm. Nucleus.

Post-translational modifications. Ubiquitinated by PRKN. ‘Lys-48’-linked polyubiquitination by PRKN leads to degradation by the proteasome and may play a key role in regulation of neuron death.

Miscellaneous. May act as a downstream effector of PRKN and contribute to neurodegeneration in Parkinson disease cases caused by defects in PRKN: its accumulation due to the absence of PRKN, followed by up-regulation of PPARGC1A, could lead to the selective loss of dopamine neurons in the substantia nigra.

Similarity. Belongs to the krueppel C2H2-type zinc-finger protein family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q6NUN9-1	1	yes
Q6NUN9-2	2
Q6NUN9-3	3

RefSeq proteins (4): NP_001156946, NP_001350446, NP_001381127, NP_689770 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001909	KRAB	Domain
IPR013087	Znf_C2H2_type	Domain
IPR036051	KRAB_dom_sf	Homologous_superfamily
IPR036236	Znf_C2H2_sf	Homologous_superfamily

Pfam: PF00096, PF01352

UniProt features (27 total): mutagenesis site 8, compositionally biased region 4, zinc finger region 4, region of interest 4, cross-link 2, splice variant 2, chain 1, domain 1, coiled-coil region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6NUN9-F1	52.30	0.08

Functional residue map

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

Post-translational modifications (2): 282, 286

Mutagenesis-validated functional residues (8):

Position	Phenotype
458	no effect.
471	no effect.
518	no effect.
528	no effect.
543	no effect.
560	no effect.
571	impairs dna-binding and ability to repress pgc-1-alpha (ppargc1a).
584	no effect.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-212436	Generic Transcription Pathway

MSigDB gene sets: 103 (showing top): GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GAUSSMANN_MLL_AF4_FUSION_TARGETS_A_DN, SANSOM_APC_TARGETS_UP, TGTTTAC_MIR30A5P_MIR30C_MIR30D_MIR30B_MIR30E5P, GOBP_PROTEIN_HOMOOLIGOMERIZATION, GOBP_PROTEIN_HETEROOLIGOMERIZATION, SANSOM_APC_TARGETS, MYB_Q6, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, GOBP_NEGATIVE_REGULATION_OF_TRANSCRIPTION_BY_RNA_POLYMERASE_II, GOBP_NEGATIVE_REGULATION_OF_NUCLEOBASE_CONTAINING_COMPOUND_METABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_TRANSCRIPTION_BY_RNA_POLYMERASE_II, BYSTRYKH_HEMATOPOIESIS_STEM_CELL_QTL_TRANS, GOBP_PROTEIN_COMPLEX_OLIGOMERIZATION, KUMAR_PATHOGEN_LOAD_BY_MACROPHAGES

GO Biological Process (6): negative regulation of transcription by RNA polymerase II (GO:0000122), negative regulation of DNA-templated transcription (GO:0045892), positive regulation of transcription by RNA polymerase II (GO:0045944), protein homooligomerization (GO:0051260), protein heterooligomerization (GO:0051291), regulation of DNA-templated transcription (GO:0006355)

GO Molecular Function (9): transcription cis-regulatory region binding (GO:0000976), RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription repressor activity, RNA polymerase II-specific (GO:0001227), DNA-binding transcription factor activity (GO:0003700), zinc ion binding (GO:0008270), DNA binding (GO:0003677), protein binding (GO:0005515), ubiquitin protein ligase binding (GO:0031625), metal ion binding (GO:0046872)

GO Cellular Component (4): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
RNA Polymerase II Transcription	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
regulation of transcription by RNA polymerase II	2
transcription by RNA polymerase II	2
DNA-templated transcription	2
regulation of DNA-templated transcription	2
protein complex oligomerization	2
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
negative regulation of DNA-templated transcription	1
negative regulation of RNA biosynthetic process	1
positive regulation of DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
transcription regulatory region nucleic acid binding	1
sequence-specific double-stranded DNA binding	1
cis-regulatory region sequence-specific DNA binding	1
negative regulation of transcription by RNA polymerase II	1
DNA-binding transcription factor activity, RNA polymerase II-specific	1
DNA-binding transcription repressor activity	1
transcription cis-regulatory region binding	1
transcription regulator activity	1
transition metal ion binding	1
nucleic acid binding	1
binding	1
ubiquitin-like protein ligase binding	1
cation binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

1488 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZNF746	PRKN	O60260	791
ZNF746	PPARGC1A	Q9UBK2	745
ZNF746	TRIM28	Q13263	632
ZNF746	AIMP2	Q13155	606
ZNF746	PINK1	Q9BXM7	581
ZNF746	NRF1	Q16656	526
ZNF746	PARK7	Q99497	447
ZNF746	SNCA	P37840	445
ZNF746	MFN2	O95140	435
ZNF746	NPM1	P06748	429
ZNF746	TFAM	Q00059	428
ZNF746	MFN1	Q8IWA4	417
ZNF746	ZBTB1	Q9Y2K1	413
ZNF746	SGSM3	Q96HU1	408
ZNF746	PARL	Q9H300	378

IntAct

67 interactions, top by confidence:

A	B	Type	Score
NPHP1	NPHP4	psi-mi:“MI:0914”(association)	0.930
PPP2R2C	PPP2R1A	psi-mi:“MI:0914”(association)	0.730
PRKN	ZNF746	psi-mi:“MI:0915”(physical association)	0.590
ZNF746	PRKN	psi-mi:“MI:0915”(physical association)	0.590
N	NOP56	psi-mi:“MI:0914”(association)	0.530
N	RBM47	psi-mi:“MI:0914”(association)	0.530
ZNF324B	ZNF316	psi-mi:“MI:0914”(association)	0.530
EIF3L	EIF3CL	psi-mi:“MI:0914”(association)	0.530
KLHL40	CBX4	psi-mi:“MI:0914”(association)	0.530
ZNF398	LRP4	psi-mi:“MI:0914”(association)	0.530
ZNF746		psi-mi:“MI:0407”(direct interaction)	0.440
	ZNF746	psi-mi:“MI:0407”(direct interaction)	0.440
CCL26	ZNF746	psi-mi:“MI:0915”(physical association)	0.370
DIABLO	ZNF746	psi-mi:“MI:0915”(physical association)	0.370
ZNF746	DUSP23	psi-mi:“MI:0915”(physical association)	0.370
EPHA8	ZNF746	psi-mi:“MI:0915”(physical association)	0.370
ZNF746	FAM118B	psi-mi:“MI:0915”(physical association)	0.370
FES	ZNF746	psi-mi:“MI:0915”(physical association)	0.370
GSK3B	ZNF746	psi-mi:“MI:0915”(physical association)	0.370
ZNF746	HMOX2	psi-mi:“MI:0915”(physical association)	0.370
ZNF746	ILK	psi-mi:“MI:0915”(physical association)	0.370
MAP3K7	ZNF746	psi-mi:“MI:0915”(physical association)	0.370
PRKRA	ZNF746	psi-mi:“MI:0915”(physical association)	0.370
RPS6KA6	ZNF746	psi-mi:“MI:0915”(physical association)	0.370
ZNF746	MAP3K20	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (348): ZNF746 (Affinity Capture-MS), RPL23AP5 (Affinity Capture-MS), MYO1C (Affinity Capture-MS), POLRMT (Affinity Capture-MS), IGF2BP3 (Affinity Capture-MS), NOP56 (Affinity Capture-MS), DDX3X (Affinity Capture-MS), IRS4 (Affinity Capture-MS), EIF3D (Affinity Capture-MS), DHX15 (Affinity Capture-MS), PSMD3 (Affinity Capture-MS), HNRNPR (Affinity Capture-MS), TIMM44 (Affinity Capture-MS), AP1G1 (Affinity Capture-MS), MYO1B (Affinity Capture-MS)

ESM2 similar proteins: A0A0J9YXV3, A0A172M4N0, A2VE23, A5PL33, C7EMF5, E7EW31, F1NSM7, I3L273, O15027, O48582, O55189, O55196, O97939, P0C671, P0DV77, P14138, Q14D33, Q1XI13, Q28989, Q3B7M4, Q4R729, Q5R7U0, Q5SWP3, Q62840, Q63003, Q6E0U4, Q6H236, Q6NUN9, Q6UXA7, Q7Z2K8, Q86UU5, Q8BM15, Q8K4E0, Q8K4L6, Q8N1P7, Q8N3D4, Q96D09, Q96JG9, Q9BGL9, Q9D7G9

Diamond homologs: A2A761, A6NFI3, A6NK75, A6NM28, A6NP11, A6QPT6, A8MQ14, A8MTY0, A8MUV8, B4DU55, B4DX44, B4DXR9, O60290, O75373, O75437, O95780, P0DPD5, P17014, P17032, P35789, P51523, P52736, P52738, Q02525, Q03923, Q03936, Q05481, Q06730, Q06732, Q14587, Q14593, Q14929, Q15928, Q16587, Q2KI58, Q3B7M4, Q3SXZ3, Q3U133, Q49AA0, Q4R6C2

SIGNOR signaling

8 interactions.

A	Effect	B	Mechanism
PRKN	“down-regulates quantity by destabilization”	ZNF746	polyubiquitination
PINK1	“down-regulates quantity by destabilization”	ZNF746	phosphorylation
PRKN	“down-regulates quantity by destabilization”	ZNF746	ubiquitination
ABL1	“up-regulates activity”	ZNF746	phosphorylation
ZNF746	“up-regulates quantity by expression”	PPARGC1A	“transcriptional regulation”
PINK1	“up-regulates activity”	ZNF746	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 65 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.

GO biological processes:

GO term	Partners	Fold	FDR
transcription by RNA polymerase II	7	8.2×	8e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	74
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1375 predictions. Top by Δscore:

Variant	Effect	Δscore
7:149477559:CTTA:C	donor_loss	1.0000
7:149477560:TTA:T	donor_loss	1.0000
7:149477561:TA:T	donor_loss	1.0000
7:149477562:A:AC	donor_gain	1.0000
7:149477562:ACC:A	donor_loss	1.0000
7:149477563:C:A	donor_loss	1.0000
7:149477563:C:CC	donor_gain	1.0000
7:149477751:CGAGC:C	acceptor_gain	1.0000
7:149477753:AGCC:A	acceptor_loss	1.0000
7:149477756:C:CC	acceptor_gain	1.0000
7:149487144:C:CA	donor_gain	1.0000
7:149492854:CTTA:C	donor_loss	1.0000
7:149492856:TACCT:T	donor_loss	1.0000
7:149492857:A:AC	donor_gain	1.0000
7:149492858:C:CC	donor_gain	1.0000
7:149492858:C:CG	donor_loss	1.0000
7:149492968:GTAGT:G	acceptor_gain	1.0000
7:149492969:TAGT:T	acceptor_gain	1.0000
7:149492970:AGT:A	acceptor_gain	1.0000
7:149492971:GT:G	acceptor_gain	1.0000
7:149492973:C:CC	acceptor_gain	1.0000
7:149492973:CTG:C	acceptor_loss	1.0000
7:149492974:T:G	acceptor_loss	1.0000
7:149493983:CCTTA:C	donor_loss	1.0000
7:149493984:CTTA:C	donor_loss	1.0000
7:149493985:TTACC:T	donor_loss	1.0000
7:149493986:TA:T	donor_loss	1.0000
7:149493987:A:AC	donor_gain	1.0000
7:149493987:AC:A	donor_gain	1.0000
7:149493988:C:CC	donor_gain	1.0000

AlphaMissense

4283 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:149474567:G:C	H584Q	1.000
7:149474567:G:T	H584Q	1.000
7:149474569:G:C	H584D	1.000
7:149474569:G:T	H584N	1.000
7:149474577:A:G	L581P	1.000
7:149474590:G:T	R577S	1.000
7:149474594:G:C	F575L	1.000
7:149474594:G:T	F575L	1.000
7:149474595:A:G	F575S	1.000
7:149474596:A:G	F575L	1.000
7:149474606:G:C	C571W	1.000
7:149474607:C:G	C571S	1.000
7:149474607:C:T	C571Y	1.000
7:149474608:A:G	C571R	1.000
7:149474608:A:T	C571S	1.000
7:149474615:G:C	C568W	1.000
7:149474616:C:T	C568Y	1.000
7:149474617:A:G	C568R	1.000
7:149474621:G:C	F566L	1.000
7:149474621:G:T	F566L	1.000
7:149474623:A:G	F566L	1.000
7:149474639:G:C	H560Q	1.000
7:149474639:G:T	H560Q	1.000
7:149474641:G:C	H560D	1.000
7:149474646:C:G	R558P	1.000
7:149474651:G:C	H556Q	1.000
7:149474651:G:T	H556Q	1.000
7:149474652:T:G	H556P	1.000
7:149474653:G:C	H556D	1.000
7:149474653:G:T	H556N	1.000

dbSNP variants (sampled 300 via entrez): RS1000157041 (7:149478188 A>G,T), RS1000358673 (7:149477130 A>C), RS1000382149 (7:149473495 T>C), RS1000489056 (7:149479903 TAAAC>T), RS1000678 (7:149494477 C>T), RS1000698949 (7:149475710 T>C), RS1000976830 (7:149475502 C>A,T), RS1001020475 (7:149495600 A>G), RS1001047362 (7:149481805 T>A), RS1001060575 (7:149488687 T>G), RS1001117599 (7:149474422 G>A,C), RS1001160563 (7:149477139 TC>T,TCC), RS1001342041 (7:149486921 A>C,T), RS1001499890 (7:149479752 A>G,T), RS1001533675 (7:149495910 G>A)

Disease associations

OMIM: gene MIM:613914 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST000406_13	Amyotrophic lateral sclerosis	4.000000e-08
GCST001198_42	Multiple sclerosis	5.000000e-09

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases expression	4
sodium arsenite	affects cotreatment, increases abundance, increases expression	2
Air Pollutants	increases abundance, increases expression, affects expression	2
Formaldehyde	decreases expression, increases expression	2
Tobacco Smoke Pollution	increases expression	2
Valproic Acid	affects expression, increases methylation	2
Cyclosporine	increases expression	2
TAK-243	increases sumoylation	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects expression	1
lead acetate	increases expression	1
sulforaphane	increases expression	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
cupric chloride	increases expression	1
beta-methylcholine	affects expression	1
glycidamide	increases expression	1
pinostrobin	increases expression	1
PCI 5002	affects cotreatment, increases expression	1
Acetaminophen	affects expression	1
Arsenic	increases abundance, increases expression, affects cotreatment	1
Azathioprine	increases expression	1
Doxorubicin	decreases expression	1
Ethyl Methanesulfonate	increases expression	1
Manganese	increases abundance, increases expression, affects cotreatment	1
Methyl Methanesulfonate	increases expression	1
Ozone	affects expression, increases abundance	1
Silver	increases expression	1
Smoke	increases abundance, increases expression	1
Thiram	increases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_TZ45	HAP1 ZNF746 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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