ZNF384

protein-coding

zinc finger protein 384, the group of Zinc fingers C2H2-type

Gene summary

This gene encodes a C2H2-type zinc finger protein, which may function as a transcription factor. This gene also contains long CAG trinucleotide repeats that encode consecutive glutamine residues. The protein appears to bind and regulate the promoters of the extracellular matrix genes MMP1, MMP3, MMP7 and COL1A1. Studies in mouse suggest that nuclear matrix transcription factors (NP/NMP4) may be part of a general mechanical pathway that couples cell construction and function during extracellular matrix remodeling. Alternative splicing results in multiple transcript variants. Recurrent rearrangements of this gene with the Ewing's sarcoma gene, EWSR1 on chromosome 22, or with the TAF15 gene on chromosome 17, or with the TCF3 (E2A) gene on chromosome 19, have been observed in acute leukemia. A related pseudogene has been identified on chromosome 7. [provided by RefSeq, Apr 2011]

Previous symbols:

TNRC1

MANE transcript

NM_001385745.1

Inheritance

—

ClinVar variants

U:67B:4

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.07

Max pathogenic AF

—

Genomic locus

chr12:6,666,477-6,689,572

External References & Databases

Ensembl (ENSG00000126746)

Transcript & Mutation Effects

hg38 • Region Span ~23.1 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ZNF384 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 64

not providedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001385745.1. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				4 clinvar		4
missense			63 clinvar			63
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	0	0	67	4	0	71

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 98 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001385745.1	RefSeq	NP_001372674.1	10	MANE Select
ENST00000683879.1	Ensembl	ENSP00000507462.1	10	MANE Select
NM_001039920.3	RefSeq	NP_001035009.1	7	Standard
NM_001135734.3	RefSeq	NP_001129206.1	9	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

regulation of transcription by RNA polymerase II

Molecular Function

DNA-binding transcription factor activity, RNA polymerase II-specific
DNA binding
metal ion binding

Cellular Component

nucleus

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000396801
Coding exons: 9
Length: 23096
Individuals with no LoFs: 125742
Homozygous LoFs: 0
Heterozygous LoFs: 4
Defined: 125746
p: 0.0000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.44	212	338	0.627	0.0000193	3746
Missense (PolyPhen)		59	140.71	0.4193		1536
Synonymous	-1.42	159	138	1.15	0.00000827	1151
Loss of Function	4.52	2	27.6	0.0724	0.00000128	315

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.0000092	0.0000088	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Transcription factor that binds the consensus DNA sequence [GC]AAAAA. Seems to bind and regulate the promoters of MMP1, MMP3, MMP7 and COL1A1 (By similarity). {ECO:0000250}.;

Recessive Scores

pRec: 0.130

Intolerance Scores

LoFtool: 0.197
RVIS EVS: -0.78
RVIS percentile EVS: 12.88

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.998

Gene Damage Prediction

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