ZNF462

Summary

ZNF462 (zinc finger protein 462, HGNC:21684) is a protein-coding gene on chromosome 9q31.2, encoding Zinc finger protein 462 (Q96JM2). Zinc finger nuclear factor involved in transcription by regulating chromatin structure and organization. It is haploinsufficient (ClinGen: sufficient evidence).

The protein encoded by this gene belongs to C2H2-type zinc finger family of proteins. It contains multiple C2H2-type zinc fingers and may be involved in transcriptional regulation. Alternative splicing results in multiple transcript variants encoding different isoforms.

Source: NCBI Gene 58499 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Weiss-Kruszka syndrome (Definitive, ClinGen)
• GWAS associations: 35
• Clinical variants (ClinVar): 703 total — 55 pathogenic, 26 likely-pathogenic
• Phenotypes (HPO): 50
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_021224

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21684
Approved symbol	ZNF462
Name	zinc finger protein 462
Location	9q31.2
Locus type	gene with protein product
Status	Approved
Aliases	DKFZP762N2316, KIAA1803, Zfp462
Ensembl gene	ENSG00000148143
Ensembl biotype	protein_coding
OMIM	617371
Entrez	58499

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 7 protein_coding_CDS_not_defined, 6 protein_coding

ENST00000277225, ENST00000374686, ENST00000427098, ENST00000441147, ENST00000469433, ENST00000471032, ENST00000472574, ENST00000479166, ENST00000480607, ENST00000482115, ENST00000483287, ENST00000497489, ENST00000902271

RefSeq mRNA: 2 — MANE Select: NM_021224 NM_001347997, NM_021224

CCDS: CCDS35096

Canonical transcript exons

ENST00000277225 — 13 exons

Exon	Start	End
ENSE00000983391	107003294	107003426
ENSE00000983392	107009545	107009668
ENSE00001023580	106932446	106932549
ENSE00001464341	107010823	107013634
ENSE00001633746	106924133	106929759
ENSE00001865652	106863166	106863355
ENSE00003496333	106984186	106984409
ENSE00003498280	106935503	106935621
ENSE00003650488	106972005	106972272
ENSE00003655885	106930525	106930689
ENSE00003685240	106974137	106974273
ENSE00003693857	106938916	106939107
ENSE00003701112	106923354	106923603

Expression profiles

Bgee: expression breadth ubiquitous, 258 present calls, max score 96.92.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 3.4714 / max 146.3959, expressed in 1010 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
97873	3.4537	1010
97881	0.0145	3
97880	0.0032	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	96.92	gold quality
oviduct epithelium	UBERON:0004804	95.09	gold quality
corpus callosum	UBERON:0002336	94.38	gold quality
kidney epithelium	UBERON:0004819	93.73	gold quality
medial globus pallidus	UBERON:0002477	93.46	gold quality
inferior vagus X ganglion	UBERON:0005363	93.12	gold quality
globus pallidus	UBERON:0001875	92.97	gold quality
sural nerve	UBERON:0015488	92.96	gold quality
cortical plate	UBERON:0005343	92.61	gold quality
ventral tegmental area	UBERON:0002691	92.15	gold quality
ganglionic eminence	UBERON:0004023	92.14	gold quality
embryo	UBERON:0000922	92.13	gold quality
subthalamic nucleus	UBERON:0001906	91.29	gold quality
nipple	UBERON:0002030	91.08	gold quality
lateral globus pallidus	UBERON:0002476	91.03	gold quality
tibia	UBERON:0000979	90.84	gold quality
calcaneal tendon	UBERON:0003701	90.74	gold quality
upper arm skin	UBERON:0004263	90.68	gold quality
dorsal root ganglion	UBERON:0000044	90.67	gold quality
tendon	UBERON:0000043	90.59	gold quality
medulla oblongata	UBERON:0001896	90.45	gold quality
sperm	CL:0000019	90.39	gold quality
dorsal plus ventral thalamus	UBERON:0001897	90.37	gold quality
substantia nigra pars reticulata	UBERON:0001966	89.97	gold quality
substantia nigra pars compacta	UBERON:0001965	89.91	gold quality
lateral nuclear group of thalamus	UBERON:0002736	89.60	gold quality
superior vestibular nucleus	UBERON:0007227	89.59	gold quality
tendon of biceps brachii	UBERON:0008188	89.59	gold quality
ventricular zone	UBERON:0003053	89.51	gold quality
parotid gland	UBERON:0001831	89.39	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-HCAD-35	yes	59.67
E-GEOD-84465	yes	22.94
E-HCAD-25	yes	16.37
E-ANND-3	yes	8.96
E-GEOD-93593	yes	4.27
E-CURD-97	no	82.73

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CTCF

miRNA regulators (miRDB)

49 targeting ZNF462, 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-5692A	100.00	74.40	6850
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-520F-3P	99.82	71.32	1216
HSA-MIR-26A-5P	99.78	73.52	2303
HSA-MIR-26B-5P	99.78	73.51	2305
HSA-MIR-548AG	99.77	69.25	1492
HSA-MIR-1825	99.72	68.11	1089
HSA-MIR-4465	99.71	72.56	2096
HSA-MIR-1208	99.70	68.28	1533
HSA-MIR-548AI	99.69	69.24	1494
HSA-MIR-548BA	99.69	69.14	1514
HSA-MIR-570-5P	99.69	69.24	1494
HSA-MIR-646	99.68	67.84	1645
HSA-MIR-1251-3P	99.64	67.21	1408
HSA-MIR-4743-3P	99.62	68.12	2095
HSA-MIR-6073	99.60	70.36	793
HSA-MIR-17-3P	99.55	66.77	1311
HSA-MIR-7844-5P	99.55	68.56	1428
HSA-MIR-510-3P	99.54	70.06	2965
HSA-MIR-186-3P	99.51	66.24	1685
HSA-MIR-6740-3P	99.48	68.49	1392
HSA-MIR-942-5P	99.41	68.40	1977

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 6)

• Zinc finger protein 462 (ZNF462) is the first human O-GlcNAc-6-phosphate modified protein. (PMID:22826440)
• Loss of function variants in ZNF462 were identified in patients with ptosis, metopic ridging, craniosynostosis, dysgenesis of the corpus callosum, and developmental delay. (PMID:28513610)
• In the current study we describe a patient with a syndromic form of autism spectrum disorder and intellectual disability characterized by metopic craniosynostosis, ptosis and corpus callosum dysgenesis most likely caused by ZNF462 haploinsufficiency. The possible contribution of the disruption of KLF12 by one of the translocation breakpoints remains unclear. (PMID:29427787)
• a multiple congenital anomaly syndrome associated with haploinsufficiency of ZNF462 that has distinct clinical characteristics and facial features, is reported. (PMID:31361404)
• Further characterization of the 9q31 microdeletion phenotype; delineation of a common region of overlap containing ZNF462. (PMID:36461789)
• Phenotypic spectrum in Weiss-Kruszka syndrome caused by ZNF462 variants: Three new patients and literature review. (PMID:39069253)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	ZNF462	ENSDARG00000112909
mus_musculus	Zfp462	ENSMUSG00000060206
rattus_norvegicus	Zfp462	ENSRNOG00000032048
drosophila_melanogaster	CG12769	FBGN0033252
caenorhabditis_elegans		WBGENE00001223
caenorhabditis_elegans		WBGENE00017406
caenorhabditis_elegans		WBGENE00019960

Paralogs (7): ZNF423 (ENSG00000102935), ZNF211 (ENSG00000121417), ZBTB39 (ENSG00000166860), ZNF597 (ENSG00000167981), ZNF445 (ENSG00000185219), ZNF786 (ENSG00000197362), ZNF521 (ENSG00000198795)

Protein

Protein identifiers

Zinc finger protein 462 — Q96JM2 (reviewed: Q96JM2)

Alternative names: Zinc finger PBX1-interacting protein

All UniProt accessions (4): Q96JM2, H0Y6H9, H3BLX4, U3KQU3

UniProt curated annotations — full annotation on UniProt →

Function. Zinc finger nuclear factor involved in transcription by regulating chromatin structure and organization. Involved in the pluripotency and differentiation of embryonic stem cells by regulating SOX2, POU5F1/OCT4, and NANOG. By binding PBX1, prevents the heterodimerization of PBX1 and HOXA9 and their binding to DNA. Regulates neuronal development and neural cell differentiation.

Subunit / interactions. Interacts with PBX1; this interaction prevents PBX1-HOXA9 heterodimer from forming and binding to DNA.

Subcellular location. Nucleus.

Post-translational modifications. O-GlcNAcylated with O-GlcNAc-6-phosphate.

Disease relevance. Weiss-Kruszka syndrome (WSKA) [MIM:618619] An autosomal dominant, multiple congenital anomaly syndrome with variable expressivity and complete penetrance. Patients manifest developmental delay, hypotonia, feeding difficulties, craniofacial abnormalities including ptosis, abnormal head shape, downslanting palpebral fissures, metopic ridging, and craniosynostosis. Variable congenital heart defects can be observed in some patients. A few patients show agenesis of the corpus callosum on brain imaging. The disease is caused by variants affecting the gene represented in this entry.

Isoforms (3)

UniProt ID	Names	Canonical?
Q96JM2-1	1	yes
Q96JM2-2	2
Q96JM2-3	3

RefSeq proteins (2): NP_001334926, NP_067047* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013087	Znf_C2H2_type	Domain
IPR036236	Znf_C2H2_sf	Homologous_superfamily
IPR050688	Zinc_finger/UBP_domain	Family
IPR057830	Znf_C2H2_ZNF462_N	Domain
IPR057831	Znf_C2H2_ZNF462_1st	Domain
IPR057832	Znf_C2H2_ZNF462_2nd	Domain
IPR059058	Znf-C2H2_ZNF462	Domain
IPR059059	Znf-C2H2_7th_ZNF462	Domain

Pfam: PF23075, PF23077, PF23223, PF23224, PF23225

UniProt features (106 total): cross-link 30, zinc finger region 27, sequence variant 12, sequence conflict 8, region of interest 8, modified residue 8, strand 3, compositionally biased region 3, splice variant 3, glycosylation site 2, chain 1, helix 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
1X6F	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96JM2-F1	50.74	0.01

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 (38): 849, 350, 354, 688, 1090, 1166, 2004, 2172, 2177, 20, 20, 234, 271, 337, 347, 349, 428, 484, 631, 657 …

Glycosylation sites (2): 292, 309

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 222 (showing top): CMYB_01, AREB6_03, GCM_ZNF198, ACTGCAG_MIR173P, GGGTGGRR_PAX4_03, MOLENAAR_TARGETS_OF_CCND1_AND_CDK4_UP, GARGALOVIC_RESPONSE_TO_OXIDIZED_PHOSPHOLIPIDS_BLUE_DN, TGCTGAY_UNKNOWN, TGTGTGA_MIR377, SCHAEFFER_PROSTATE_DEVELOPMENT_6HR_DN, E4F1_Q6, SCHAEFFER_PROSTATE_DEVELOPMENT_AND_CANCER_BOX4_DN, TURASHVILI_BREAST_DUCTAL_CARCINOMA_VS_DUCTAL_NORMAL_DN, LYF1_01, AFP1_Q6

GO Biological Process (2): chromatin organization (GO:0006325), positive regulation of transcription by RNA polymerase II (GO:0045944)

GO Molecular Function (4): DNA binding (GO:0003677), zinc ion binding (GO:0008270), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (2): nucleus (GO:0005634), nucleoplasm (GO:0005654)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular component organization	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
nucleic acid binding	1
transition metal ion binding	1
binding	1
cation binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1006 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZNF462	ASXL2	Q76L83	914
ZNF462	VAX1	Q5SQQ9	898
ZNF462	ZNF483	Q8TF39	684
ZNF462	RAD23B	P54727	473
ZNF462	TMEM38B	Q9NVV0	471
ZNF462	EXD1	Q8NHP7	466
ZNF462	RPRD2	Q5VT52	449
ZNF462	ZNF292	O60281	448
ZNF462	UBE3B	Q7Z3V4	425
ZNF462	ZNF573	Q86YE8	419
ZNF462	PBX1	P40424	410
ZNF462	HAO1	Q9UJM8	404
ZNF462	ZDHHC24	Q6UX98	396
ZNF462	PTPDC1	A2A3K4	395
ZNF462	STARD9	Q9P2P6	394

IntAct

34 interactions, top by confidence:

A	B	Type	Score
ZNF462	EHMT2	psi-mi:“MI:0915”(physical association)	0.740
DPY30	AKAP8	psi-mi:“MI:0914”(association)	0.610
ZNF462	WIZ	psi-mi:“MI:0914”(association)	0.530
XAGE2	WIZ	psi-mi:“MI:0914”(association)	0.530
ABHD10	UBR5	psi-mi:“MI:0914”(association)	0.530
CBX1	ZNF292	psi-mi:“MI:0914”(association)	0.530
ZNF462	TCOF1	psi-mi:“MI:0915”(physical association)	0.400
CFTR	ZNF462	psi-mi:“MI:0915”(physical association)	0.370
NEK4	E2F8	psi-mi:“MI:0914”(association)	0.350
SOX2	CBX4	psi-mi:“MI:0914”(association)	0.350
ANKRA2	RFXAP	psi-mi:“MI:0914”(association)	0.350
CTBP1	TAF15	psi-mi:“MI:0914”(association)	0.350
CTBP1	GSN	psi-mi:“MI:0914”(association)	0.350
	ARID1A	psi-mi:“MI:0914”(association)	0.350
CBX5	ZNF568	psi-mi:“MI:0914”(association)	0.350
ABHD10	VWA8	psi-mi:“MI:0914”(association)	0.350
ABHD10	GAPDHS	psi-mi:“MI:0914”(association)	0.350
PPP2R2B	ARHGAP10	psi-mi:“MI:0914”(association)	0.350
CBX3	MYL12B	psi-mi:“MI:0914”(association)	0.350
CBX5	ZNF292	psi-mi:“MI:0914”(association)	0.350
ZNF462	CALU	psi-mi:“MI:0914”(association)	0.350
FEV	TAF4	psi-mi:“MI:2364”(proximity)	0.270
HNF4A	TAF4	psi-mi:“MI:2364”(proximity)	0.270
PAX6	SMCHD1	psi-mi:“MI:2364”(proximity)	0.270
SOX2	SMCHD1	psi-mi:“MI:2364”(proximity)	0.270
TEAD1	SMCHD1	psi-mi:“MI:2364”(proximity)	0.270
TLX1	BCL9	psi-mi:“MI:2364”(proximity)	0.270
ZMYM2	ZBTB5	psi-mi:“MI:2364”(proximity)	0.270
ZNF462	EHMT2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (101): ZNF462 (Affinity Capture-MS), ZNF462 (Affinity Capture-MS), WIZ (Affinity Capture-MS), EHMT1 (Affinity Capture-MS), EHMT2 (Affinity Capture-MS), D2HGDH (Affinity Capture-MS), ZNF644 (Affinity Capture-MS), CBX5 (Affinity Capture-MS), ZNF462 (Affinity Capture-RNA), ZNF462 (Biochemical Activity), ZNF462 (Affinity Capture-MS), ZNF462 (Affinity Capture-MS), ZNF462 (Affinity Capture-MS), AIFM1 (Affinity Capture-MS), CALU (Affinity Capture-MS)

ESM2 similar proteins: A2T7S4, A5GFT6, B1AWL2, B3DJM5, D3ZKB9, F1QLG5, G5EFY7, H2KYH4, H2L008, O13089, O15164, O42410, O73590, P70121, P81183, Q0VEE6, Q13422, Q14B70, Q2HNT1, Q2HNT2, Q2TB10, Q4R6F6, Q5DTH5, Q5RDQ6, Q5XJV7, Q5ZKW8, Q63HK5, Q64127, Q68FE9, Q6PJT7, Q6ZN30, Q6ZPY5, Q6ZSZ6, Q7Z353, Q86UP3, Q8BMQ3, Q8CCH7, Q8CGV9, Q8R515, Q8TCN5

Diamond homologs: B1AWL2, Q02031, Q02033, Q96JM2, P31504, P31505, P31506, Q01777, Q01789, Q01790, Q02029, Q02030, Q02032, Q25514, A2ANX9, A7Y7X5, O75362, P10925, P15822, P20662, P80944, Q03172, Q29419, Q7JM44, Q8WUU4, Q95LI3, Q99PV8, Q9C0K0, Q9H165, Q9QYE3, Q9Y462, A2A884, P31629, Q00900, Q3UHF7, Q5T1R4, Q6B4Z5, Q7TSH3, Q92618, Q9P243

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
ZNF462	“down-regulates activity”	PBX1	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	55
Likely pathogenic	26
Uncertain significance	421
Likely benign	144
Benign	20

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1076643	NM_021224.6(ZNF462):c.1872_1875del (p.Phe625fs)	Pathogenic
1275771	NM_021224.6(ZNF462):c.2859del (p.Asn954fs)	Pathogenic
1285511	NM_021224.6(ZNF462):c.3700C>T (p.Arg1234Ter)	Pathogenic
1299321	NM_021224.6(ZNF462):c.220+1G>A	Pathogenic
1343244	NM_021224.6(ZNF462):c.2029del (p.Arg677fs)	Pathogenic
1449443	NM_021224.6(ZNF462):c.5974C>T (p.Gln1992Ter)	Pathogenic
1676126	NM_021224.6(ZNF462):c.5531_5544del (p.Leu1844fs)	Pathogenic
1705000	NM_021224.6(ZNF462):c.4745_4746del (p.Cys1582fs)	Pathogenic
1706559	NM_021224.6(ZNF462):c.3111dup (p.Ala1038fs)	Pathogenic
1709341	NM_021224.6(ZNF462):c.4825dup (p.Ser1609fs)	Pathogenic
1803088	NM_021224.6(ZNF462):c.5941C>T (p.Arg1981Ter)	Pathogenic
1879740	NM_021224.6(ZNF462):c.2283G>A (p.Trp761Ter)	Pathogenic
1992398	NM_021224.6(ZNF462):c.3937del (p.His1313fs)	Pathogenic
2499557	NM_021224.6(ZNF462):c.718C>T (p.Arg240Ter)	Pathogenic
2500924	NM_021224.6(ZNF462):c.3502dup (p.Arg1168fs)	Pathogenic
2631549	NM_021224.6(ZNF462):c.6163C>T (p.Arg2055Ter)	Pathogenic
2671805	NM_021224.6(ZNF462):c.1690C>T (p.Gln564Ter)	Pathogenic
2671806	NM_021224.6(ZNF462):c.1151del (p.Asn384fs)	Pathogenic
2671807	NM_021224.6(ZNF462):c.507C>A (p.Tyr169Ter)	Pathogenic
2671810	NM_021224.6(ZNF462):c.2726del (p.His909fs)	Pathogenic
3027495	NM_021224.6(ZNF462):c.5323C>T (p.Gln1775Ter)	Pathogenic
3254949	NM_021224.6(ZNF462):c.1937_1940del (p.Asp646fs)	Pathogenic
3258178	NM_021224.6(ZNF462):c.6146_6150dup (p.His2051fs)	Pathogenic
3342256	NM_021224.6(ZNF462):c.6696-2A>C	Pathogenic
3359072	NM_021224.6(ZNF462):c.1975C>T (p.Gln659Ter)	Pathogenic
3376290	NM_021224.6(ZNF462):c.3111_3131delinsA (p.Phe1037fs)	Pathogenic
3377166	NM_021224.6(ZNF462):c.2987del (p.Arg996fs)	Pathogenic
3476082	NM_021224.6(ZNF462):c.2022_2023insTTGTAA (p.Ala675delinsLeuTer)	Pathogenic
3476083	NM_021224.6(ZNF462):c.3603del (p.Asn1202fs)	Pathogenic
3476088	NM_021224.6(ZNF462):c.1992del (p.Leu665fs)	Pathogenic

SpliceAI

2824 predictions. Top by Δscore:

Variant	Effect	Δscore
9:106863352:TTCT:T	donor_gain	1.0000
9:106863353:TCTGT:T	donor_loss	1.0000
9:106863354:CTGT:C	donor_loss	1.0000
9:106863355:TG:T	donor_loss	1.0000
9:106863356:G:GG	donor_gain	1.0000
9:106863356:GTAA:G	donor_loss	1.0000
9:106863357:TAAG:T	donor_loss	1.0000
9:106923348:CCACA:C	acceptor_loss	1.0000
9:106923349:CACAG:C	acceptor_loss	1.0000
9:106923351:CAGGT:C	acceptor_loss	1.0000
9:106923352:A:T	acceptor_loss	1.0000
9:106923353:G:GA	acceptor_loss	1.0000
9:106923600:TCAG:T	donor_loss	1.0000
9:106923604:G:A	donor_loss	1.0000
9:106923605:T:G	donor_loss	1.0000
9:106932550:G:GG	donor_gain	1.0000
9:106935483:T:A	acceptor_gain	1.0000
9:106935495:A:AG	acceptor_gain	1.0000
9:106935497:A:AG	acceptor_gain	1.0000
9:106935498:T:G	acceptor_gain	1.0000
9:106935498:TCAAG:T	acceptor_loss	1.0000
9:106935499:CAAGT:C	acceptor_loss	1.0000
9:106935500:A:AG	acceptor_gain	1.0000
9:106935500:AAGTT:A	acceptor_loss	1.0000
9:106935501:A:C	acceptor_loss	1.0000
9:106935501:A:G	acceptor_gain	1.0000
9:106935501:AGTTT:A	acceptor_gain	1.0000
9:106935502:G:GA	acceptor_gain	1.0000
9:106935502:GT:G	acceptor_gain	1.0000
9:106935502:GTTT:G	acceptor_gain	1.0000

AlphaMissense

16712 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:106923399:T:A	C6S	1.000
9:106923399:T:C	C6R	1.000
9:106923400:G:A	C6Y	1.000
9:106923400:G:C	C6S	1.000
9:106923401:T:G	C6W	1.000
9:106923408:T:A	C9S	1.000
9:106923408:T:C	C9R	1.000
9:106923409:G:A	C9Y	1.000
9:106923409:G:C	C9S	1.000
9:106923410:T:G	C9W	1.000
9:106923439:T:A	L19H	1.000
9:106923439:T:C	L19P	1.000
9:106924240:T:A	C110S	1.000
9:106924240:T:C	C110R	1.000
9:106924241:G:A	C110Y	1.000
9:106924241:G:C	C110S	1.000
9:106924242:C:G	C110W	1.000
9:106924249:T:A	C113S	1.000
9:106924249:T:C	C113R	1.000
9:106924250:G:A	C113Y	1.000
9:106924250:G:C	C113S	1.000
9:106924250:G:T	C113F	1.000
9:106924251:T:G	C113W	1.000
9:106924261:T:C	F117L	1.000
9:106924263:C:A	F117L	1.000
9:106924263:C:G	F117L	1.000
9:106924280:T:C	L123P	1.000
9:106924402:T:A	C164S	1.000
9:106924402:T:C	C164R	1.000
9:106924403:G:A	C164Y	1.000

dbSNP variants (sampled 300 via entrez): RS1000026639 (9:106941211 T>C), RS1000057157 (9:106869739 A>G), RS1000070096 (9:106970969 A>C), RS1000070520 (9:106895520 C>T), RS1000109307 (9:106953659 T>C), RS1000115729 (9:107001318 A>G), RS1000120462 (9:106983637 A>C), RS1000152 (9:106925007 T>C), RS1000159746 (9:106864899 T>C), RS1000179757 (9:106920216 C>T), RS1000182581 (9:106947257 A>G), RS1000186443 (9:106906705 C>T), RS1000218150 (9:106871114 T>C), RS1000224347 (9:106902313 T>G), RS1000225692 (9:107006551 G>A)

Disease associations

OMIM: gene MIM:617371 | disease phenotypes: MIM:618619, MIM:114480, MIM:123100, MIM:156200

GenCC curated gene-disease

Disease	Classification	Inheritance
Weiss-Kruszka syndrome	Definitive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
Weiss-Kruszka syndrome	Definitive	AD

Mondo (6): Weiss-Kruszka syndrome (MONDO:0032836), cleft lip (MONDO:0004747), hereditary breast carcinoma (MONDO:0016419), craniosynostosis (MONDO:0015469), intellectual disability, autosomal dominant (MONDO:0100172), primary ovarian failure (MONDO:0005387)

Orphanet (4): Weiss-Kruszka Syndrome (Orphanet:502430), Hereditary breast cancer (Orphanet:227535), Craniosynostosis (Orphanet:1531), NON RARE IN EUROPE: Primary ovarian failure (Orphanet:619)

HPO phenotypes

50 total (30 of 50 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000028	Cryptorchidism
HP:0000286	Epicanthus
HP:0000289	Broad philtrum
HP:0000316	Hypertelorism
HP:0000356	Abnormality of the outer ear
HP:0000365	Hearing impairment
HP:0000369	Low-set ears
HP:0000378	Cupped ear
HP:0000396	Overfolded helix
HP:0000411	Protruding ear
HP:0000463	Anteverted nares
HP:0000494	Downslanted palpebral fissures
HP:0000508	Ptosis
HP:0000729	Autistic behavior
HP:0000750	Delayed speech and language development
HP:0000824	Decreased response to growth hormone stimulation test
HP:0000954	Single transverse palmar crease
HP:0001252	Hypotonia
HP:0001256	Mild intellectual disability
HP:0001270	Motor delay
HP:0001274	Agenesis of corpus callosum
HP:0001290	Generalized hypotonia
HP:0001627	Abnormal heart morphology
HP:0001629	Ventricular septal defect
HP:0001647	Bicuspid aortic valve
HP:0001712	Left ventricular hypertrophy
HP:0001804	Hypoplastic fingernail
HP:0002079	Hypoplasia of the corpus callosum
HP:0002119	Ventriculomegaly

GWAS associations

35 associations (top):

Study	Trait	p-value
GCST000175_42	Height	2.000000e-08
GCST000404_1	Menarche (age at onset)	2.000000e-09
GCST000817_173	Height	2.000000e-13
GCST002177_6	Adverse response to chemotherapy in breast cancer (alopecia) (anti-microtubule)	2.000000e-06
GCST002945_24	Emphysema imaging phenotypes	1.000000e-07
GCST003061_4	Cutaneous malignant melanoma	7.000000e-11
GCST003075_13	Cognitive decline rate in late mild cognitive impairment	4.000000e-07
GCST003075_136	Cognitive decline rate in late mild cognitive impairment	6.000000e-07
GCST003993_20	Menarche (age at onset)	2.000000e-34
GCST003994_12	Age at voice drop	2.000000e-10
GCST004562_233	Waist circumference adjusted for body mass index	5.000000e-08
GCST004563_196	Waist circumference adjusted for BMI (joint analysis main effects and physical activity interaction)	7.000000e-08
GCST006061_81	Atrial fibrillation	4.000000e-09
GCST006482_17	Lung function (FEV1/FVC)	2.000000e-08
GCST006482_18	Lung function (FEV1/FVC)	1.000000e-06
GCST006630_18	Diastolic blood pressure	7.000000e-11
GCST006661_84	Male-pattern baldness	7.000000e-09
GCST006921_6	Regular attendance at a pub or social club	9.000000e-09
GCST007323_28	Risk-taking tendency (4-domain principal component model)	2.000000e-08
GCST007327_16	Smoking status (ever vs never smokers)	2.000000e-08
GCST007576_103	Chronotype	4.000000e-10
GCST008163_76	Height	6.000000e-06
GCST008757_11	Alcohol consumption	2.000000e-13
GCST008811_30	Alcohol consumption (drinks per week)	7.000000e-09
GCST008839_482	Height	8.000000e-19
GCST008839_565	Height	3.000000e-11
GCST009066_18	Mosaic loss of chromosome Y (Y chromosome dosage)	2.000000e-09
GCST010002_276	Refractive error	1.000000e-15
GCST010703_166	Brain morphology (MOSTest)	4.000000e-09
GCST010796_592	Electrocardiogram morphology (amplitude at temporal datapoints)	9.000000e-09

EFO canonical traits (19, from GWAS)

EFO ID	Trait name
EFO:0004703	age at menarche
EFO:0005260	response to antimicrotubule agent
EFO:0007626	emphysema imaging measurement
EFO:0007710	cognitive decline measurement
EFO:0007888	age at voice drop
EFO:0007789	BMI-adjusted waist circumference
EFO:0008002	physical activity measurement
EFO:0004713	FEV/FVC ratio
EFO:0006336	diastolic blood pressure
EFO:0009592	social interaction measurement
EFO:0008579	risk-taking behaviour
EFO:0004318	smoking behavior
EFO:0008328	chronotype measurement
EFO:0007783	mosaic loss of chromosome Y measurement
EFO:0004346	neuroimaging measurement
EFO:0004327	electrocardiography
EFO:0009819	comparative body size at age 10, self-reported
EFO:0008039	BMI-adjusted hip circumference
EFO:0004305	erythrocyte count

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D002971	Cleft Lip	C07.465.409.225; C07.465.525.164; C07.650.525.164; C16.131.850.525.164
D003398	Craniosynostoses	C05.116.099.370.894.232; C05.660.207.240; C05.660.906.364; C16.131.621.207.240; C16.131.621.906.364
D016649	Primary Ovarian Insufficiency	C12.050.351.500.056.630.750; C12.100.250.056.630.750; C19.391.630.750
C562840	Breast Cancer, Familial (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, affects cotreatment, decreases expression	5
Benzo(a)pyrene	decreases methylation, increases expression, decreases expression	4
Calcitriol	increases expression, affects cotreatment	3
sodium arsenite	increases abundance, decreases expression, affects cotreatment	2
Tobacco Smoke Pollution	decreases expression, affects response to substance	2
Cyclosporine	decreases expression, increases methylation	2
Cadmium Chloride	decreases expression, increases expression	2
GSK-J4	increases expression	1
FR900359	affects phosphorylation	1
TAK-243	decreases sumoylation	1
bisphenol A	increases methylation	1
arsenite	affects binding, decreases reaction	1
sulforaphane	decreases expression	1
cobaltous chloride	decreases expression	1
manganese chloride	decreases expression, increases abundance, affects cotreatment	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	affects cotreatment, decreases expression	1
(+)-JQ1 compound	affects expression, increases reaction	1
Sunitinib	decreases expression	1
Panobinostat	affects expression, increases reaction	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Atrazine	decreases expression	1
Cisplatin	affects cotreatment, decreases expression	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Doxorubicin	decreases expression	1
Estradiol	increases expression	1
Hydrogen Peroxide	affects expression	1

Cellosaurus cell lines

3 cell lines: 3 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A8H7	SEES3-1V human ZNF462, clone1	Embryonic stem cell	Male
CVCL_A8H8	SEES3-1V human ZNF462, clone2	Embryonic stem cell	Male
CVCL_A8H9	SEES3-1V human ZNF462, clone3	Embryonic stem cell	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03480607	PHASE4	COMPLETED	Dexmedetomidine as Adjuvant for Bupivacaine in Ultrasound Guided Infraorbital Nerve Block for Cleft Lip Repair
NCT00722436	PHASE4	TERMINATED	Tranexamic Acid for Craniofacial Surgery
NCT02188576	PHASE4	COMPLETED	The Efficacy and Population Pharmacokinetics of Tranexamic Acid for Craniosynostosis Surgery
NCT00417066	PHASE4	COMPLETED	Flexible GnRH Antagonist vs Flare up GnRH Agonist Protocol in Poor Responders
NCT00732693	PHASE4	COMPLETED	Evaluation of Physiologic and Standard Sex Steroid Replacement Regimens in Women With Premature Ovarian Failure
NCT00837616	PHASE4	COMPLETED	Estrogen Dosing in Turner Syndrome: Pharmacology and Metabolism
NCT01853501	PHASE4	UNKNOWN	Effects of ADSC Therapy in Women With POF
NCT02783937	PHASE4	COMPLETED	Filgrastim for Premature Ovarian Insufficiency
NCT03535480	PHASE4	UNKNOWN	Autologous Bone Marrow Stem Cell Ovarian Transplantation to Restore Ovarian Function in Premature Ovarian Failure
NCT00098319	PHASE3	COMPLETED	Oral Cleft Prevention Trial in Brazil
NCT00397917	PHASE3	COMPLETED	Oral Cleft Prevention Program
NCT03314090	PHASE3	COMPLETED	Silicone Gel in the Treatment of Cleft Lip Scars
NCT00140998	PHASE3	COMPLETED	Estrogen Treatment (Oral vs. Patches) in Turner Syndrome
NCT00004639	PHASE2	COMPLETED	Cleft Palate Surgery and Speech Development
NCT06885801	PHASE2	NOT_YET_RECRUITING	Evaluation of a Novel Nasal Conformer in Pediatric Patients
NCT02229968	PHASE2	ACTIVE_NOT_RECRUITING	Efficacy of Amicar for Children Having Craniofacial Surgery
NCT00001951	PHASE2	COMPLETED	Hormone Replacement in Young Women With Premature Ovarian Failure
NCT00370019	PHASE2	WITHDRAWN	Effects of an Estrogen Replacement Therapy Skin Patch on Ovulation in Women With Premature Ovarian Failure
NCT00429494	PHASE2	COMPLETED	GnRH Analogue for Ovarian Function Preservation in Hematopoietic Stem Cell Transplantation Patients
NCT03816852	PHASE2	SUSPENDED	The Safety and Efficiency Study of Mesenchymal Stem Cell (19#iSCLife®-POI) in Premature Ovarian Insufficiency
NCT04536467	PHASE2	UNKNOWN	Prevention of Chemotherapy-Induced Ovarian Failure With Goserelin in Premenopausal Lymphoma Patients
NCT06117982	PHASE2	COMPLETED	The Impact of Granulocyte Colony Stimulating Factor on Premature Ovarian Insufficiency
NCT06765837	PHASE1	COMPLETED	Comparison Between Low Level Laser Therapy and Active Oxygen Releasing Gel on Wound Healing Cleft Lip Patients
NCT00912119	PHASE1	COMPLETED	Amicar Pharmacokinetics of Children Having Craniofacial Surgery
NCT02912104	PHASE1	COMPLETED	A Therapeutic Trial of Human Amniotic Epithelial Cells Transplantation for Primary Ovarian Failure
NCT03178695	PHASE1	COMPLETED	Inovium Ovarian Rejuvenation Trials
NCT04815213	PHASE1	ACTIVE_NOT_RECRUITING	The Use of Expandeded Mesenchymal Stromal Cells (MSC) in Premature Ovarian Failure (POF) in Adult Humans
NCT05138367	PHASE1	COMPLETED	Effects of UCA-PSCs in Women With POF
NCT06132542	PHASE1	UNKNOWN	Autologous ADMSC Transplantation in Patients With POI
NCT02247193	PHASE1/PHASE2	COMPLETED	Botulinum Toxin to Improve Cosmesis of Primary Cleft Lip Repair
NCT00070811	Not specified	COMPLETED	Assessing the Results of Lip Surgery in Patients With Cleft Lip and Palate
NCT00097149	Not specified	COMPLETED	Systematic Pediatric Care for Oral Clefts - South America
NCT00213889	Not specified	TERMINATED	TWIST Human Gene and Cleft Lips and Palates
NCT00285714	Not specified	UNKNOWN	3D Imaging of Hard and Soft Tissue in Orthognathic Surgery
NCT00340977	Not specified	COMPLETED	Svangerskap, Arv, Og Miljo (Pregnancy, Heredity and Environment)
NCT00829101	Not specified	COMPLETED	Articulation and Phonology in Children With Unilateral Cleft Lip and Palate
NCT00975208	Not specified	UNKNOWN	Osteogenesis and Dental Eruption Through Electrical Stimuli
NCT01252264	Not specified	COMPLETED	FaceBase Biorepository
NCT01380171	Not specified	COMPLETED	Primary Palatoplasty in Pediatric Patients - A Retrospective Review of Surgical Outcomes
NCT01601171	Not specified	RECRUITING	Genetics of Reproductive Disorders (Including Kallmann Syndrome) and Cleft Lip and/or Palate