ZNF469

protein-coding

zinc finger protein 469, the group of Zinc fingers C2H2-type

Gene summary

This gene encodes a zinc-finger protein. Low-percent homology to certain collagens suggests that it may function as a transcription factor or extra-nuclear regulator factor for the synthesis or organization of collagen fibers. Mutations in this gene cause brittle cornea syndrome. [provided by RefSeq, Jul 2008]

MANE transcript

NM_001367624.2

Inheritance

AR, AD

ClinVar variants

P:201U:2375B:2821

Top phenotype

Brittle cornea syndrome 1

gnomAD constraint

pLI —, LoF o/e 0.2

Max pathogenic AF

—

Genomic locus

chr16:88,382,959-88,440,757

External References & Databases

Ensembl (ENSG00000225614)

Transcript & Mutation Effects

hg38 • Region Span ~57.8 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

brittle cornea syndrome 1STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0024543

Submitter: PanelApp Australia

aortic disorderLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0005561

Submitter: Ambry Genetics

brittle cornea syndrome 1STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0024543

Submitter: Labcorp Genetics (formerly Invitae)

brittle cornea syndromeSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0009242

Submitter: Orphanet

brittle cornea syndrome 1DEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0024543

Submitter: G2P

brittle cornea syndrome 1STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0024543

Submitter: Genomics England PanelApp

Clinical Genomic Database (CGD)

Brittle cornea syndrome 1AR

Manifestation: Musculoskeletal; Ophthalmologic

Intervention: Ophthalmologic

Rationale: Individuals are prone to ophthalmologic injury (such as corneal rupture) with minimal trauma, and protective measures may be beneficial

Refs: 13627089; 14218178; 5755738; 4872990; 5775573; 4691558; 962660; 7387950; 2112090; 2363420; 14679583; 18452888; 19661234; 20938016

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ZNF469 variants in ClinVar

19 Conditions Cataloged

not providedTotal: 3515

Cardiovascular phenotypeTotal: 3498

not specifiedTotal: 971

ZNF469-related disorderTotal: 370

Brittle cornea syndrome 1Total: 295

Ehlers-Danlos syndromeTotal: 214

Keratoconus 1Total: 33

Spontaneous hematomasTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001367624.2. 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		2 clinvar	10 clinvar	2144 clinvar	12 clinvar	2168
missense	5 clinvar	1 clinvar	2343 clinvar	646 clinvar	19 clinvar	3014
nonsense	34 clinvar	13 clinvar	6 clinvar			53
start loss			1 clinvar			1
frameshift	112 clinvar	34 clinvar	15 clinvar			161
splice donor/acceptor (+/-2bp)						0
Total	151	50	2375	2790	31	5397

Highest pathogenic variant AF is 0.00015938356

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 4 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001367624.2	RefSeq	NP_001354553.1	1	MANE Select
ENST00000565624.3	Ensembl	ENSP00000456500.2	1	MANE Select
ENST00000437464.1	Ensembl	ENSP00000402343.1	2	Standard
XM_047434810.1	RefSeq	XP_047290766.1	1	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: ENST00000437464
Coding exons: 2
Length: 13287
Individuals with no LoFs: 0
Homozygous LoFs: 0
Heterozygous LoFs: 0
Defined: 0
p: 0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.774	2188	2.29e+3	0.955	0.000147	24895
Missense (PolyPhen)		326	355.28	0.91757		4145
Synonymous	1.38	1017	1.07e+3	0.946	0.0000804	8757
Loss of Function	4.63	8	39.3	0.203	0.00000213	446

Population LoF Frequency

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

dbNSFP Gene Annotations

Source: dbNSFP

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

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Indispensability pred.: N
Indispensability score: 0.142

Gene Damage Prediction

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