ZNF674

zinc finger protein 674, the group of Zinc fingers C2H2-type

Basic information

Region (hg38): X:46497724-46545457

Previous symbols: [ "MRX92" ]

Links

ENSG00000251192 ∙ NCBI:641339 ∙ OMIM:300573 ∙ HGNC:17625 ∙ Uniprot:Q2M3X9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• intellectual disability (Disputed Evidence), mode of inheritance: XL
• X-linked intellectual disability (Disputed Evidence), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Mental retardation, X-linked 92	XL	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic	16385466; 23871722
The evidence of variants as being related to disease causation has been questioned due to subsequent population-based studies

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ZNF674 gene.

• Inborn genetic diseases (14 variants)
• not specified (8 variants)
• not provided (8 variants)
• History of neurodevelopmental disorder (1 variants)
• Non-syndromic X-linked intellectual disability (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ZNF674 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				3		3
missense			13		5	18
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			1			1
non coding			1			1
Total	0	0	14	3	5

Variants in ZNF674

This is a list of pathogenic ClinVar variants found in the ZNF674 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
X-46498721-CTA-C		Non-syndromic X-linked intellectual disability	Uncertain significance (Jun 14, 2016)
X-46499893-A-G		not specified	Uncertain significance (Aug 18, 2014)
X-46499906-T-C			Likely benign (Nov 01, 2022)
X-46499920-C-A		not specified	Uncertain significance (Nov 09, 2021)
X-46499955-C-A		ZNF674-related disorder	Likely benign (Apr 14, 2023)
X-46500034-G-T			Uncertain significance (Apr 25, 2023)
X-46500129-T-C			Uncertain significance (-)
X-46500238-C-T		not specified	Uncertain significance (Feb 27, 2024)
X-46500265-C-A		ZNF674-related disorder	Likely benign (Feb 21, 2022)
X-46500294-T-C		not specified • ZNF674-related disorder	Benign (Jun 07, 2019)
X-46500372-A-G		not specified	Benign (Apr 10, 2013)
X-46500464-A-C		not specified • ZNF674-related disorder	Benign (Jun 07, 2019)
X-46500505-G-T		not specified	Benign/Likely benign (-)
X-46500524-C-G		not specified	Uncertain significance (Aug 12, 2021)
X-46500560-C-T		ZNF674-related disorder	Likely benign (Sep 23, 2019)
X-46500561-G-A		not specified • ZNF674-related disorder	Benign (Jul 15, 2019)
X-46500597-A-G		not specified	Uncertain significance (Nov 07, 2023)
X-46500597-ATG-A		not specified	Conflicting classifications of pathogenicity (Apr 01, 2020)
X-46500653-T-A		not specified	Uncertain significance (Dec 22, 2023)
X-46500690-C-T		not specified • ZNF674-related disorder	Benign (Dec 31, 2019)
X-46500705-A-G		not specified	Uncertain significance (Jun 06, 2023)
X-46500750-T-C		not specified	Uncertain significance (Feb 10, 2022)
X-46500801-T-C		not specified	Uncertain significance (Jun 23, 2023)
X-46500810-G-T		not specified	Uncertain significance (Sep 01, 2021)
X-46500823-C-T		not specified	Uncertain significance (Nov 10, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ZNF674	protein_coding	protein_coding	ENST00000523374	4	47731

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
6.04e-7	0.452	125068	235	424	125727	0.00262

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.06	156	198	0.789	0.0000133	3861
Missense in Polyphen		48	65.237	0.73578		1283
Synonymous	0.550	66	71.9	0.917	0.00000530	1015
Loss of Function	0.717	11	13.9	0.792	9.54e-7	307

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00456	0.00393
Ashkenazi Jewish	0.00600	0.00418
East Asian	0.000446	0.000326
Finnish	0.00131	0.000878
European (Non-Finnish)	0.00677	0.00393
Middle Eastern	0.000446	0.000326
South Asian	0.00281	0.00154
Other	0.00426	0.00277

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May be involved in transcriptional regulation.

Intolerance Scores

• loftool: 0.810
• rvis_EVS: 1.04
• rvis_percentile_EVS: 91.26

Haploinsufficiency Scores

• pHI: 0.215
• hipred: N
• hipred_score: 0.148
• ghis: 0.414

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.00277

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Gene ontology

• Biological process: regulation of transcription by RNA polymerase II;negative regulation of transcription, DNA-templated
• Cellular component: nucleus
• Molecular function: DNA-binding transcription factor activity, RNA polymerase II-specific;DNA binding;metal ion binding