ZNF644

protein-coding

zinc finger protein 644, the group of Zinc fingers C2H2-type

Gene summary

The protein encoded by this gene is a zinc finger transcription factor that may play a role in eye development. Defects in this gene have been associated with high myopia. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Aug 2011]

MANE transcript

NM_201269.3

Inheritance

ClinVar variants

P:2U:183B:43

Top phenotype

Myopia 21, autosomal dominant

gnomAD constraint

pLI —, LoF o/e 0.13

Max pathogenic AF

—

Genomic locus

chr1:90,915,298-91,022,272

External References & Databases

Ensembl (ENSG00000122482)

Transcript & Mutation Effects

hg38 • Region Span ~107.0 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

myopia 21, autosomal dominantLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0013604

Submitter: Ambry Genetics

myopia 21, autosomal dominantSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0013604

Submitter: PanelApp Australia

myopia 21, autosomal dominantLIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0013604

Submitter: Labcorp Genetics (formerly Invitae)

myopia 21, autosomal dominantLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0013604

Submitter: Laboratory for Molecular Medicine

This gene-disease relationship has undergone rapid assessment. Classifications are based on preliminary review of gene-disease validity during analysis of genomic sequencing results.

Clinical Genomic Database (CGD)

Myopia 21, autosomal dominantAD

Manifestation: Ophthalmologic

Intervention: General

Rationale: 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

Refs: 21695231

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ZNF644 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 185

not providedTotal: 27

ZNF644-related disorderTotal: 21

Myopia 21, autosomal dominantTotal: 10

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_201269.3. 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			1 clinvar	21 clinvar	4 clinvar	26
missense	2 clinvar		176 clinvar	11 clinvar	7 clinvar	196
nonsense			3 clinvar			3
start loss						0
frameshift			3 clinvar			3
splice donor/acceptor (+/-2bp)						0
Total	2	0	183	32	11	228

Highest pathogenic variant AF is 0.000014869133

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 45 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_201269.3	RefSeq	NP_958357.1	5	MANE Select
ENST00000337393.10	Ensembl	ENSP00000337008.5	5	MANE Select
NM_001437610.1	RefSeq	NP_001424539.1	5	Standard
NM_001437611.1	RefSeq	NP_001424540.1	5	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
znf644b	Danio rerio	Structure: retina Quality: increased occurrence abnormal

Gene / Model

Organism

Observed Phenotype

znf644b

Danio rerio

Structure: retina

Quality: increased occurrence

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

regulation of transcription, DNA-templated
regulation of transcription by RNA polymerase II

Molecular Function

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

Cellular Component

nucleus

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000370440
Coding exons: 5
Length: 106971
Individuals with no LoFs: 125727
Homozygous LoFs: 0
Heterozygous LoFs: 16
Defined: 125743
p: 0.0000636

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.55	548	660	0.830	0.0000341	8774
Missense (PolyPhen)		165	270.63	0.6097		3551
Synonymous	-0.303	247	241	1.02	0.0000127	2455
Loss of Function	5.53	6	46.9	0.128	0.00000282	683

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.00016	0.00014	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.000055	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000027	0.000026	rare
South Asian	0.000098	0.000098	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

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

Recessive Scores

pRec: 0.103

Intolerance Scores

LoFtool: 0.238
RVIS EVS: -0.32
RVIS percentile EVS: 30.94

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.908

Gene Damage Prediction

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