NM_014009.4(FOXP3):c.751_753del (p.Glu251del) AND Insulin-dependent diabetes mellitus secretory diarrhea syndrome

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Mar 26, 2022
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV000012166.14

Allele description [Variation Report for NM_014009.4(FOXP3):c.751_753del (p.Glu251del)]

NM_014009.4(FOXP3):c.751_753del (p.Glu251del)

Gene:

FOXP3:forkhead box P3 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

Xp11.23

Genomic location:

Preferred name:

NM_014009.4(FOXP3):c.751_753del (p.Glu251del)

Other names:

E203del

HGVS:

NC_000023.11:g.49255494_49255496del
NG_007392.1:g.14334_14336del
NG_021311.2:g.25030_25032del
NM_001114377.2:c.646_648del
NM_014009.3:c.751_753del
NM_014009.4:c.751_753delMANE SELECT
NP_001107849.1:p.Glu216del
NP_054728.2:p.Glu251del
LRG_62t1:c.751_753del
LRG_62:g.14334_14336del
NC_000023.10:g.49111953_49111955del
NC_000023.10:g.49111955_49111957del

Protein change:

E216del; GLU203DEL

Links:

OMIM: 300292.0007; dbSNP: rs122467171

NCBI 1000 Genomes Browser:

rs122467171

Molecular consequence:

NM_001114377.2:c.646_648del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_014009.4:c.751_753del - inframe_deletion - [Sequence Ontology: SO:0001822]

Condition(s)

Name:: Insulin-dependent diabetes mellitus secretory diarrhea syndrome (IPEX)
Synonyms:: DIABETES MELLITUS, CONGENITAL INSULIN-DEPENDENT, WITH FATAL SECRETORY DIARRHEA; IMMUNODEFICIENCY, POLYENDOCRINOPATHY, AND ENTEROPATHY, X-LINKED; X-linked autoimmunity-allergic dysregulation syndrome; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0010580; MedGen: C0342288; Orphanet: 37042; OMIM: 304790

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Rbm4 RNA binding motif protein 4 [Mus musculus]
Rbm4 RNA binding motif protein 4 [Mus musculus]
Gene ID:19653

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000032400	OMIM	no assertion criteria provided	Pathogenic (Dec 1, 2000)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV003444660	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Mar 26, 2022)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 17586580, 11120765, 20537998, 24916357, 30443250, 32531870, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000032400

OMIM

no assertion criteria provided

Pathogenic
(Dec 1, 2000)

germline

literature only

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

SCV003444660

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Mar 26, 2022)

germline

clinical testing

PubMed (7)
[See all records that cite these PMIDs]

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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

FOXP3 is a homo-oligomer and a component of a supramolecular regulatory complex disabled in the human XLAAD/IPEX autoimmune disease.

Li B, Samanta A, Song X, Iacono KT, Brennan P, Chatila TA, Roncador G, Banham AH, Riley JL, Wang Q, Shen Y, Saouaf SJ, Greene MI.

Int Immunol. 2007 Jul;19(7):825-35. Epub 2007 Jun 22.

PubMed [citation]

PMID:: 17586580

JM2, encoding a fork head-related protein, is mutated in X-linked autoimmunity-allergic disregulation syndrome.

Chatila TA, Blaeser F, Ho N, Lederman HM, Voulgaropoulos C, Helms C, Bowcock AM.

J Clin Invest. 2000 Dec;106(12):R75-81.

PubMed [citation]

PMID:: 11120765
PMCID:: PMC387260

See all PubMed Citations (7)

Details of each submission

From OMIM, SCV000032400.1

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

Description

In a kindred with IPEX (304790), Chatila et al. (2000) found that affected males were hemizygous for a deletion of 3 bp in exon 7 of the FOXP3 gene, resulting in loss of the glutamic acid-201 residue.

#	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 Labcorp Genetics (formerly Invitae), Labcorp, SCV003444660.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (7)

Description

ClinVar contains an entry for this variant (Variation ID: 11413). For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this variant affects FOXP3 function (PMID: 17586580). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. This variant has been observed in individuals with clinical features of X-linked recessive immunodysregulation, polyendocrinopathy, and enteropathy (IPEX syndrome) (PMID: 11120765, 20537998, 24916357, 30443250, 32531870). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This variant, c.751_753del, results in the deletion of 1 amino acid(s) of the FOXP3 protein (p.Glu251del), but otherwise preserves the integrity of the reading frame.

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

Last Updated: Oct 20, 2024

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