ZNF750

protein-coding

zinc finger protein 750

Gene summary

This gene encodes a protein with a nuclear localization site and a C2H2 zinc finger domain. Mutations in this gene have been associated with seborrhea-like dermatitis with psoriasiform elements. [provided by RefSeq, Jul 2008]

MANE transcript

NM_024702.3

Inheritance

AD, AR

ClinVar variants

P:1U:127B:38

Top phenotype

Seborrhea-like dermatitis with psoriasiform elements

gnomAD constraint

pLI —, LoF o/e 0.13

Max pathogenic AF

—

Genomic locus

chr17:82,829,434-82,840,022

External References & Databases

Ensembl (ENSG00000141579)

Transcript & Mutation Effects

hg38 • Region Span ~10.6 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

seborrhea-like dermatitis with psoriasiform elementsSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0012446

Submitter: Orphanet

seborrhea-like dermatitis with psoriasiform elementsLIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0012446

Submitter: Labcorp Genetics (formerly Invitae)

seborrhea-like dermatitis with psoriasiform elementsLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0012446

Submitter: PanelApp Australia

seborrhea-like dermatitis with psoriasiform elementsLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0012446

Submitter: LiferaOmics

Genetic evidence – Published (AR scope) No scorable published cases of biallelic (autosomal recessive) ZNF750 variants causing seborrhea-like dermatitis with psoriasiform elements were identified. Published genetic evidence total = 0 / 12 Published (AD context; not scored for AR) ZNF750-related seborrhea-like dermatitis with psoriasiform elements has been reported in an autosomal dominant context with heterozygous variants. This evidence is not scorable under the autosomal recessive model. AD-context evidence total (not scored for AR) = 0 Genetic evidence – Our case Family 1 – one proband. Case-level (AR homozygous; predicted null nonsense; AR predicted null default = 1.5; consanguinity not reported → no deduction applied) = 1.5; Segregation = 0; Case-control = 0 Family 1 total = 1.5 Total genetic evidence (Published AR + Our case) 1.5 / 12 Experimental evidence – Published (biological plausibility only; conservative) ZNF750 encodes a transcription factor required for epidermal differentiation and keratinocyte maturation. Functional studies demonstrate that loss of ZNF750 disrupts terminal differentiation programs and epidermal barrier gene expression, supporting a role in skin homeostasis. Function (gene role in epidermal differentiation; biological plausibility only) = 0.5 Experimental evidence total = 0.5 / 6 Overall score Genetic evidence = 1.5 Experimental evidence = 0.5 Total = 2.0

seborrhea-like dermatitis with psoriasiform elementsMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0012446

Submitter: G2P

Clinical Genomic Database (CGD)

Seborrhea-like dermatitis with psoriasiform elementsAD

Manifestation: Dermatologic

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: 16751772

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ZNF750 variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 139

not providedTotal: 22

ZNF750-related disorderTotal: 7

Seborrhea-like dermatitis with psoriasiform elementsTotal: 5

Early-onset progressive diffuse brain atrophy-microcephaly-muscle weakness-optic atrophy syndromeTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_024702.3. 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	14 clinvar	3 clinvar	18
missense			124 clinvar	16 clinvar	5 clinvar	145
nonsense						0
start loss						0
frameshift	1 clinvar		1 clinvar			2
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	1	0	127	30	8	166

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 5 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_024702.3	RefSeq	NP_078978.2	2	MANE Select
ENST00000269394.4	Ensembl	ENSP00000269394.3	2	MANE Select
ENST00000572562.1	Ensembl	ENSP00000458389.1	2	Standard
ENST00000572562.2	Ensembl	ENSP00000458389.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Gene expression (Transcription)
Generic Transcription Pathway
RNA Polymerase II Transcription

Biological Process

epidermis development
cell differentiation
positive regulation of transcription by RNA polymerase II

Molecular Function

RNA polymerase II proximal promoter sequence-specific DNA binding
DNA-binding transcription activator activity, RNA polymerase II-specific
protein binding
metal ion binding
promoter-specific chromatin binding

Cellular Component

nucleus

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000269394
Coding exons: 2
Length: 11144
Individuals with no LoFs: 125740
Homozygous LoFs: 0
Heterozygous LoFs: 8
Defined: 125748
p: 0.0000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.0697	427	423	1.01	0.0000274	4651
Missense (PolyPhen)		97	127.63	0.76		1546
Synonymous	-0.917	215	199	1.08	0.0000159	1573
Loss of Function	3.16	2	15.4	0.130	8.28e-7	188

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.00012	0.00012	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.000047	0.000046	rare
European (Non-Finnish)	0.000026	0.000026	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Transcription factor involved in epidermis differentiation. Required for terminal epidermal differentiation: acts downstream of p63/TP63 and activates expression of late epidermal differentiation genes. Specifically binds to the promoter of KLF4 and promotes its expression. {ECO:0000269|PubMed:22364861}.;
Disease: DISEASE: Seborrhea-like dermatitis with psoriasiform elements (SLDP) [MIM:610227]: Characterized by a chronic fine diffuse scaly erythematous rash on the face, particularly on the chin, nasolabial folds and eyebrows, around earlobes and over the scalp. The rash exacerbate in the winter, with emotional stress and after strenuous physical activity. Hyperkeratosis of skin over the elbows, knees, palms, soles and metacarpophalangeal joints is evident. There is no arthralgia, arthritis or neurological disorders. {ECO:0000269|PubMed:16751772}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.0889

Intolerance Scores

LoFtool: 0.368
RVIS EVS: 0.32
RVIS percentile EVS: 72.81

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.0419

Gene Damage Prediction

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