ZNF81

zinc finger protein 81, the group of Zinc fingers C2H2-type

Basic information

Region (hg38): X:47836901-48002561

Previous symbols: [ "MRX45" ]

Links

ENSG00000197779 ∙ NCBI:347344 ∙ OMIM:314998 ∙ HGNC:13156 ∙ Uniprot:P51508 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• non-syndromic X-linked intellectual disability (Supportive), mode of inheritance: XL
• intellectual disability, X-linked 45 (Limited), mode of inheritance: Unknown
• 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 45	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	Craniofacial; Musculoskeletal; Neurologic	10398246; 15121780; 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 ZNF81 gene.

• Inborn genetic diseases (22 variants)
• not specified (17 variants)
• not provided (9 variants)
• Non-syndromic X-linked intellectual disability (5 variants)
• History of neurodevelopmental disorder (3 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ZNF81 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			1	2	4	7
missense			22	3	5	30
nonsense						0
start loss						0
frameshift			1			1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			5	1		6
Total	0	0	29	6	9

Variants in ZNF81

This is a list of pathogenic ClinVar variants found in the ZNF81 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-47846258-C-T		not specified	Uncertain significance (May 04, 2020)
X-47846275-C-T		not specified • History of neurodevelopmental disorder	Benign (Dec 27, 2012)
X-47846279-C-T		not specified	Uncertain significance (Jun 29, 2015)
X-47846285-C-T		not specified	Benign (Nov 24, 2014)
X-47888018-A-T		not specified	Uncertain significance (Nov 30, 2022)
X-47888073-A-G		History of neurodevelopmental disorder • ZNF81-related disorder	Benign/Likely benign (Mar 25, 2019)
X-47888091-A-G		ZNF81-related disorder	Likely benign (Feb 20, 2019)
X-47888133-C-T		not specified	Benign (Apr 01, 2013)
X-47895879-G-A			Likely benign (Sep 01, 2022)
X-47895893-A-G		not specified	Uncertain significance (Jul 25, 2023)
X-47914996-G-A		not specified	Uncertain significance (Jul 01, 2014)
X-47914996-G-T		not specified	Benign (May 06, 2016)
X-47915063-A-G		not specified • ZNF81-related disorder	Benign/Likely benign (Feb 28, 2019)
X-47915090-A-T		not specified	Uncertain significance (Oct 04, 2022)
X-47915103-A-T		not specified	Uncertain significance (Apr 07, 2022)
X-47915107-C-T			Uncertain significance (Jan 01, 2023)
X-47915111-C-T		ZNF81-related disorder	Likely benign (Mar 18, 2019)
X-47915116-A-G		not specified	Conflicting classifications of pathogenicity (May 19, 2017)
X-47915155-A-G		not specified	Uncertain significance (May 12, 2015)
X-47915182-G-A		Intellectual disability, X-linked 45	Uncertain significance (May 01, 2004)
X-47915196-C-G		History of neurodevelopmental disorder • ZNF81-related disorder	Likely benign (Jul 27, 2022)
X-47915200-C-T		not specified	Benign (Nov 08, 2015)
X-47915237-G-T		not specified	Uncertain significance (Jun 16, 2023)
X-47915244-A-C		not specified	Uncertain significance (Mar 03, 2017)
X-47915248-A-T		ZNF81-related disorder	Likely benign (Apr 29, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ZNF81	protein_coding	protein_coding	ENST00000376954	4	165660

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.554	0.445	125391	2	4	125397	0.0000239

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.42	168	229	0.735	0.0000155	4428
Missense in Polyphen		47	90.623	0.51863		1816
Synonymous	0.673	73	80.7	0.905	0.00000553	1155
Loss of Function	2.92	3	15.4	0.195	0.00000105	347

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000741	0.0000741
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.000129	0.0000924
European (Non-Finnish)	0.0000372	0.0000176
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May be involved in transcriptional regulation.
• Disease: DISEASE: Note=A chromosomal aberration involving ZNF81 is found in a severe mental retardation patient. Translocation t(X;9)(p11.23;q34.3). {ECO:0000269|PubMed:15121780}.

Recessive Scores

• pRec: 0.158

Intolerance Scores

• loftool: 0.346
• rvis_EVS: 1.57
• rvis_percentile_EVS: 95.71

Haploinsufficiency Scores

• pHI: 0.164
• hipred: N
• hipred_score: 0.197
• ghis: 0.537

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.888

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
• Cellular component: nucleus
• Molecular function: DNA-binding transcription factor activity, RNA polymerase II-specific;DNA binding;metal ion binding