ZNF674 |
- 0
Haplo
Score - 0
Triplo
Score
Gene Facts External Data Attribution
- HGNC Symbol
- ZNF674 (HGNC:17625) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
- HGNC Name
- zinc finger protein 674
- Gene type
- protein-coding gene
- Locus type
- gene with protein product
- Previous symbols
- MRX92
- Alias symbols
- ZNF673B
- %HI
- 80.29(Read more about the DECIPHER Haploinsufficiency Index)
- pLI
- 0(Read more about gnomAD pLI score)
- LOEUF
- 1.31(Read more about gnomAD LOEUF score)
- Cytoband
- Xp11.3
- Genomic Coordinates
-
GRCh37/hg19: chrX:46357160-46404856 NCBI Ensembl UCSC GRCh38/hg38: chrX:46497725-46545421 NCBI Ensembl UCSC - MANE Select Transcript
- NM_001190417.2 ENST00000683375.1 (Read more about MANE Select)
- Function
- May be involved in transcriptional regulation. (Source: Uniprot)
Dosage Sensitivity Summary (Gene)
Haploinsufficiency (HI) Score Details
-
PUBMED:
16385466
Lugtenberg et al (2006) identified a male patient with learning disabilities, retinal dystrophy, and short stature who was shown by X-chromosomal BAC array analysis to carry a deletion of approximately 1 Mb in Xp11.3, including ZNF674 and four other genes. Subsequent screening of the ZNF674 gene in 28 XLID families and 309 index patients with previous family history suggestive of X-linked inheritance resulted in the identification of a nonsense and two missense mutations in three patients, respectively. The nonsense mutation (p.E118X) was shown to fully segregate with the phenotype, with all carrier females showing skewed X-inactivation patterns. They state that 'RT-PCR analysis revealed that the p.E118X mutation is also present in the mRNA, indicating that this mutation does not lead to complete reduction of mutant mRNA. This is expected because the mutation resides in the last exon, which means that the aberrant transcript is probably not prone to nonsense-mediated decay'. Of the two missense mutations one (p.T343M) appeared to be a polymorphism and the other (p.P412L) could not be confirmed as causative.
-
PUBMED:
22126752
In 2012 Delphin et al. questioned the role of ZNF674 in ID. They reported deletions in the Xp11.3-p11.23 region including the ZNF674 and RP2 genes in two unrelated families segregating with an X-linked retinal dystrophy phenotype but not intellectual disability (totaling 9 males with deletions).
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PUBMED:
23871722
Piton et al (2013) used the National Heart, Lung, and Blood (NHLBI) cohort (' a large cohorts of adults initially selected for cardiac, lung, or metabolic phenotypes but a priori not enriched with neurological or cognitive defects') to systematically reassess the implication of 106 genes proposed to be involved in monogenic forms of XLID. They particularly questioned the implication in XLID of ten genes, including the ZNF674 gene. They analyzed the cohort data set to evaluate the presence of truncating SNVs in males in genes with a proposed implication in ID. They found two ZNF674 nonsense mutations (c.1324C>A [p.Asp442∗] and c.601G>A [p.Arg201∗]) with one variant present in 19 hemizygous males. They therefore state that ZNF674 seems unlikely to be involved in monogenic ID with high penetrance in males.
The loss-of-function and triplosensitivity ratings for genes on the X chromosome are made in the context of a male genome to account for the effects of hemizygous duplications or nullizygous deletions. In contrast, disruption of some genes on the X chromosome causes male lethality and the ratings of dosage sensitivity instead take into account the phenotype in female individuals. Factors that may affect the severity of phenotypes associated with X-linked disorders include the presence of variable copies of the X chromosome (i.e. 47,XXY or 45,X) and skewed X-inactivation in females.
Triplosensitivity (TS) Score Details
The loss-of-function and triplosensitivity ratings for genes on the X chromosome are made in the context of a male genome to account for the effects of hemizygous duplications or nullizygous deletions. In contrast, disruption of some genes on the X chromosome causes male lethality and the ratings of dosage sensitivity instead take into account the phenotype in female individuals. Factors that may affect the severity of phenotypes associated with X-linked disorders include the presence of variable copies of the X chromosome (i.e. 47,XXY or 45,X) and skewed X-inactivation in females.