NM_001031710.3(KLHL7):c.458C>T (p.Ala153Val) AND Retinitis pigmentosa 42

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Apr 29, 2021
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000001064.12

Allele description [Variation Report for NM_001031710.3(KLHL7):c.458C>T (p.Ala153Val)]

NM_001031710.3(KLHL7):c.458C>T (p.Ala153Val)

Gene:

KLHL7:kelch like family member 7 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

7p15.3

Genomic location:

Preferred name:

NM_001031710.3(KLHL7):c.458C>T (p.Ala153Val)

HGVS:

NC_000007.14:g.23140784C>T
NG_016983.2:g.40051C>T
NM_001031710.3:c.458C>TMANE SELECT
NM_018846.5:c.314C>T
NP_001026880.2:p.Ala153Val
NP_001026880.2:p.Ala153Val
NP_061334.4:p.Ala105Val
NC_000007.13:g.23180403C>T
NG_016983.1:g.40051C>T
NM_001031710.2:c.458C>T
NR_033328.2:n.831C>T
Q8IXQ5:p.Ala153Val

Protein change:

A105V; ALA153VAL

Links:

UniProtKB: Q8IXQ5#VAR_060674; OMIM: 611119.0002; dbSNP: rs137853113

NCBI 1000 Genomes Browser:

rs137853113

Molecular consequence:

NM_001031710.3:c.458C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_018846.5:c.314C>T - missense variant - [Sequence Ontology: SO:0001583]
NR_033328.2:n.831C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Observations:

Condition(s)

Name:: Retinitis pigmentosa 42 (RP42)
Identifiers:: MONDO: MONDO:0013052; MedGen: C2751986; Orphanet: 791; OMIM: 612943

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000021214	OMIM	no assertion criteria provided	Pathogenic (Sep 23, 2011)	germline	literature only	PubMed (2) [See all records that cite these PMIDs] 19520207, 21828050
SCV001428729	Institute of Human Genetics, University of Leipzig Medical Center	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Mar 4, 2020)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002761630	Genetics and Molecular Pathology, SA Pathology See additional submitters Shariant Australia, Australian Genomics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Apr 29, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000021214

OMIM

no assertion criteria provided

Pathogenic
(Sep 23, 2011)

germline

literature only

PubMed (2)
[See all records that cite these PMIDs]

SCV001428729

Institute of Human Genetics, University of Leipzig Medical Center

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Mar 4, 2020)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV002761630

Genetics and Molecular Pathology, SA Pathology

See additional submitters

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Apr 29, 2021)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Mutations in a BTB-Kelch protein, KLHL7, cause autosomal-dominant retinitis pigmentosa.

Friedman JS, Ray JW, Waseem N, Johnson K, Brooks MJ, Hugosson T, Breuer D, Branham KE, Krauth DS, Bowne SJ, Sullivan LS, Ponjavic V, Gränse L, Khanna R, Trager EH, Gieser LM, Hughbanks-Wheaton D, Cojocaru RI, Ghiasvand NM, Chakarova CF, Abrahamson M, Göring HH, et al.

Am J Hum Genet. 2009 Jun;84(6):792-800. doi: 10.1016/j.ajhg.2009.05.007.

PubMed [citation]

PMID:: 19520207
PMCID:: PMC2694974

Ubiquitin ligase activity of Cul3-KLHL7 protein is attenuated by autosomal dominant retinitis pigmentosa causative mutation.

Kigoshi Y, Tsuruta F, Chiba T.

J Biol Chem. 2011 Sep 23;286(38):33613-21. doi: 10.1074/jbc.M111.245126. Epub 2011 Aug 2.

PubMed [citation]

PMID:: 21828050
PMCID:: PMC3190939

See all PubMed Citations (3)

Details of each submission

From OMIM, SCV000021214.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (2)

Description

In affected members of 3 unrelated families from Scandinavia, North America, and the U.K. with autosomal dominant retinitis pigmentosa (RP42; 612943), Friedman et al. (2009) identified a 458C-T transition in exon 6 of the KLHL7 gene, resulting in an ala153-to-val (A153V) substitution at a highly conserved residue. The mutation was not found in 102 Scandinavian, 183 North American, or 185 U.K. controls.

Kigoshi et al. (2011) showed that the A153V substitution abrogated interaction and colocalization of KLHL7 with CUL3 (603136). KLHL7 with A153V could form heterodimers with wildtype KLHL7 and did not interfere with interaction between wildtype KLHL7 and CUL3. However, inclusion of KLHL7 with A153V reduced the apparent E3 ligase activity of the wildtype KLHL7-CUL3 complex.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Institute of Human Genetics, University of Leipzig Medical Center, SCV001428729.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		1	not provided	not provided	not provided

From Genetics and Molecular Pathology, SA Pathology, SCV002761630.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Jan 25, 2025

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