ZNF407

protein-coding

zinc finger protein 407, the group of Zinc fingers C2H2-type

Gene summary

This gene encodes a zinc finger protein whose exact function is not known. It may be involved in transcriptional regulation. Several alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]

MANE transcript

NM_017757.3

Inheritance

AD, AR

ClinVar variants

P:1U:398B:144

Top phenotype

Short stature, impaired intellectual development, microcephaly, hypotonia, and ocular anomalies

gnomAD constraint

pLI —, LoF o/e 0.03

Max pathogenic AF

—

Genomic locus

chr18:74,597,870-75,065,671

External References & Databases

Ensembl (ENSG00000215421)

Transcript & Mutation Effects

hg38 • Region Span ~467.8 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

short stature, impaired intellectual development, microcephaly, hypotonia, and ocular anomaliesMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0859198

Submitter: PanelApp Australia

complex neurodevelopmental disorderLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0100038

Submitter: Ambry Genetics

short stature, impaired intellectual development, microcephaly, hypotonia, and ocular anomaliesMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0859198

Submitter: PanelApp Australia

short stature, impaired intellectual development, microcephaly, hypotonia, and ocular anomaliesLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0859198

Submitter: G2P

neurodevelopmental disorderLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0700092

Submitter: Ambry Genetics

short stature, impaired intellectual development, microcephaly, hypotonia, and ocular anomaliesSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0859198

Submitter: Labcorp Genetics (formerly Invitae)

intellectual disabilityLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0001071

Submitter: Ambry Genetics

short stature, impaired intellectual development, microcephaly, hypotonia, and ocular anomaliesLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0859198

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Short stature, impaired intellectual development, microcephaly, hypotonia, and ocular anomaliesAR

Manifestation: Craniofacial; Musculoskeletal; Neurologic; 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: 24907849; 32737394

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ZNF407 variants in ClinVar

7 Conditions Cataloged

not specifiedTotal: 427

not providedTotal: 159

ZNF407-related disorderTotal: 58

Short stature, impaired intellectual development, microcephaly, hypotonia, and ocular anomaliesTotal: 8

See casesTotal: 4

Radioulnar synostosis-microcephaly-scoliosis syndromeTotal: 1

Neurodevelopmental delayTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_017757.3. 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			13 clinvar	80 clinvar	9 clinvar	102
missense	1 clinvar		378 clinvar	51 clinvar	4 clinvar	434
nonsense			1 clinvar			1
start loss						0
frameshift			6 clinvar			6
splice donor/acceptor (+/-2bp)						0
Total	1	0	398	131	13	543

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 20 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_017757.3	RefSeq	NP_060227.2	8	MANE Select
ENST00000299687.10	Ensembl	ENSP00000299687.4	8	MANE Select
NM_001146189.1	RefSeq	NP_001139661.1	7	Standard
NM_001146190.1	RefSeq	NP_001139662.1	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

regulation of transcription by RNA polymerase II
regulation of gene expression

Molecular Function

RNA polymerase II core promoter sequence-specific DNA binding
DNA-binding transcription factor activity, RNA polymerase II-specific
DNA binding
zinc ion binding

Cellular Component

nucleus
histone methyltransferase complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000299687
Coding exons: 8
Length: 512522
Individuals with no LoFs: 124632
Homozygous LoFs: 0
Heterozygous LoFs: 7
Defined: 124639
p: 0.0000281

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.859	1173	1.26e+3	0.932	0.0000719	14831
Missense (PolyPhen)		280	426.68	0.65623		4848
Synonymous	-2.20	565	502	1.13	0.0000329	4285
Loss of Function	7.44	2	68.4	0.0293	0.00000360	960

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.000047	0.000046	rare
European (Non-Finnish)	0.000035	0.000035	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

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

Intolerance Scores

LoFtool: 0.0482
RVIS EVS: -0.94
RVIS percentile EVS: 9.38

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.634

Gene Damage Prediction

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