NM_001126128.2(PROK2):c.101G>A (p.Cys34Tyr) AND Hypogonadotropic hypogonadism 4 with or without anosmia

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Sep 1, 2008
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

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:: RCV000144711.3

Allele description [Variation Report for NM_001126128.2(PROK2):c.101G>A (p.Cys34Tyr)]

NM_001126128.2(PROK2):c.101G>A (p.Cys34Tyr)

Gene:

PROK2:prokineticin 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

3p13

Genomic location:

Preferred name:

NM_001126128.2(PROK2):c.101G>A (p.Cys34Tyr)

HGVS:

NC_000003.12:g.71781588C>T
NG_008275.1:g.8619G>A
NM_001126128.2:c.101G>AMANE SELECT
NM_021935.4:c.101G>A
NP_001119600.1:p.Cys34Tyr
NP_068754.1:p.Cys34Tyr
NC_000003.11:g.71830739C>T
NM_001126128.1:c.101G>A
Q9HC23:p.Cys34Tyr

Protein change:

C34Y; CYS34TYR

Links:

UniProtKB: Q9HC23#VAR_072177; OMIM: 607002.0006; dbSNP: rs587777864

NCBI 1000 Genomes Browser:

rs587777864

Molecular consequence:

NM_001126128.2:c.101G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_021935.4:c.101G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Hypogonadotropic hypogonadism 4 with or without anosmia (HH4)
Synonyms:: KAL4; Kallmann syndrome 4; PROK2-Related Isolated Gonadotropin-Releasing Hormone (GnRH) Deficiency; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0012528; MedGen: C3552343; Orphanet: 478; OMIM: 610628

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000190705	OMIM	no assertion criteria provided	Pathogenic (Sep 1, 2008)	germline	literature only	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000190705

OMIM

no assertion criteria provided

Pathogenic
(Sep 1, 2008)

germline

literature only

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

Citations

PubMed

Mutations in prokineticin 2 and prokineticin receptor 2 genes in human gonadotrophin-releasing hormone deficiency: molecular genetics and clinical spectrum.

Cole LW, Sidis Y, Zhang C, Quinton R, Plummer L, Pignatelli D, Hughes VA, Dwyer AA, Raivio T, Hayes FJ, Seminara SB, Huot C, Alos N, Speiser P, Takeshita A, Van Vliet G, Pearce S, Crowley WF Jr, Zhou QY, Pitteloud N.

J Clin Endocrinol Metab. 2008 Sep;93(9):3551-9. doi: 10.1210/jc.2007-2654. Epub 2008 Jun 17.

PubMed [citation]

PMID:: 18559922
PMCID:: PMC2567850

Details of each submission

From OMIM, SCV000190705.1

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

Description

In 2 brothers with Kallmann syndrome (HH4; 610628), Cole et al. (2008) identified heterozygosity for a c.101G-A transition in exon 2 of the PROK2 gene, resulting in a cys34-to-tyr (C34Y) substitution. Their asymptomatic mother was also heterozygous for the mutation. Functional analysis in HEK293 cells demonstrated that the C34Y substitution totally abolished calcium mobilization activity, with a 1,000-fold decrease in activity at the EC50 of wildtype.

#	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

Last Updated: Apr 23, 2022

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