ZNF687

protein-coding

zinc finger protein 687, the group of Zinc fingers C2H2-type

Gene summary

This gene encodes C2H2 zinc finger protein. The encoded protein may play a role in bone differentiation and development. Mutations in this gene are the cause of Paget disease of bone-6. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Sep 2016]

MANE transcript

NM_020832.3

Inheritance

ClinVar variants

P:2U:363B:185

Top phenotype

Paget disease of bone 6

gnomAD constraint

pLI —, LoF o/e 0.15

Max pathogenic AF

—

Genomic locus

chr1:151,281,618-151,292,176

External References & Databases

Ensembl (ENSG00000143373)

Transcript & Mutation Effects

hg38 • Region Span ~10.6 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Paget disease of bone 6LIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0014792

Submitter: Ambry Genetics

Paget disease of bone 6STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0014792

Submitter: PanelApp Australia

Paget disease of bone 6LIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0014792

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Paget disease of bone 6AD

Manifestation: Musculoskeletal; Oncologic

Intervention: Oncologic

Rationale: The condition can involve malignant giant cell tumors (GCT) of the bone arising from within the Paget bone lesions, and awareness may allow early detection and management

Refs: 26849110

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ZNF687 variants in ClinVar

4 Conditions Cataloged

not providedTotal: 463

not specifiedTotal: 230

Paget disease of bone 6Total: 10

ZNF687-related disorderTotal: 5

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_020832.3. 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			5 clinvar	157 clinvar	7 clinvar	169
missense	1 clinvar	1 clinvar	349 clinvar	16 clinvar	5 clinvar	372
nonsense			3 clinvar			3
start loss						0
frameshift			4 clinvar			4
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	1	1	363	173	12	550

Highest pathogenic variant AF is 0.00019640953

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 43 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_020832.3	RefSeq	NP_065883.1	8	MANE Select
ENST00000336715.11	Ensembl	ENSP00000336620.5	8	MANE Select
NM_001304763.2	RefSeq	NP_001291692.1	8	Standard
NM_001304764.2	RefSeq	NP_001291693.1	8	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
protein binding
metal ion binding

Cellular Component

nucleoplasm
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000324048
Coding exons: 8
Length: 10563
Individuals with no LoFs: 125730
Homozygous LoFs: 0
Heterozygous LoFs: 18
Defined: 125748
p: 0.0000716

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.81	609	748	0.814	0.0000443	7961
Missense (PolyPhen)		149	257.17	0.57939		2750
Synonymous	-1.37	325	295	1.10	0.0000168	2716
Loss of Function	4.52	5	33.0	0.152	0.00000164	411

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00019	0.00018	rare
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000097	0.000088	rare
South Asian	0.00010	0.000098	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May be involved in transcriptional regulation.;
Disease: DISEASE: Paget disease of bone 6 (PDB6) [MIM:616833]: An autosomal dominant form of Paget disease, a disorder of bone remodeling characterized by increased bone turnover affecting one or more sites throughout the skeleton, primarily the axial skeleton. Osteoclastic overactivity followed by compensatory osteoblastic activity leads to a structurally disorganized mosaic of bone (woven bone), which is mechanically weaker, larger, less compact, more vascular, and more susceptible to fracture than normal adult lamellar bone. PDB6 is characterized by adult onset of bone pain associated with polyostotic bone lesions primarily affecting the axial skeleton. In some cases, the pagetic tissue undergoes neoplastic transformation, resulting in osteosarcoma and, less frequently, in giant cell tumor of bone. {ECO:0000269|PubMed:26849110}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.133

Intolerance Scores

LoFtool: 0.382
RVIS EVS: -0.81
RVIS percentile EVS: 12.08

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): H
Indispensability pred.: E
Indispensability score: 0.963

Gene Damage Prediction

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