FKRP

Chr 19AR

fukutin related protein

Also known as: FKTR, LGMD2I, LGMDR9, MDC1C, MDDGA5, MDDGB5, MDDGC5

NCBI Gene: 79147 ENSG00000181027 UniProt: Q9H9S5 OMIM: 606596

The protein is targeted to the medial Golgi apparatus and is necessary for posttranslational modification of dystroglycan. Mutations cause autosomal recessive muscular dystrophy-dystroglycanopathy with a spectrum ranging from severe congenital forms with brain and eye anomalies to milder limb-girdle presentations, often with cognitive disability and cerebellar cysts. The pathogenicity results from defective dystroglycan modification leading to impaired muscle membrane stability and brain development.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a protein which is targeted to the medial Golgi apparatus and is necessary for posttranslational modification of dystroglycan. Mutations in this gene have been associated with congenital muscular dystrophy, cognitive disability, and cerebellar cysts. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some of these variants has not been determined. [provided by RefSeq, Oct 2008]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 1.323 OMIM phenotypes

VCEP Guidelines: Limb Girdle Muscular DystrophyReleased

ClinGen Panel

Clinical Summary— FKRP

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Gene-Disease Validity (ClinGen)

myopathy caused by variation in FKRP · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

64 unique Pathogenic / Likely Pathogenic· 167 VUS of 299 total submissions

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Clinical Trials

3 active or recruiting trials — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

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GeneReview available — FKRP

Authoritative clinical overview · Recommended first read

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.32LOEUF

pLI 0.000

Z-score 0.78

OE 0.76 (0.46–1.32)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

1.85Z-score

OE missense 0.71 (0.64–0.79)

230 obs / 323.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.76 (0.46–1.32)

0≤0.351.4

Missense OE?0.71 (0.64–0.79)

0≤0.61.4

Synonymous OE?0.79

0≤1.21.6

LoF obs/exp: 9 / 11.9Missense obs/exp: 230 / 323.6Syn Z: 2.05

ClinVar Variant Classifications

299 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic21

Likely Pathogenic43

VUS167

Likely Benign60

Conflicting6

Pathogenic

Likely Pathogenic

167

VUS

Likely Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	16	3	2	0	21
Likely Pathogenic	31	12	0	0	43
VUS	2	160	2	3	167
Likely Benign	0	0	1	59	60
Benign	0	0	0	0	0
Conflicting	—				6
Total	49	175	5	62	297

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

1 pathogenic / likely-pathogenic (of 1) ClinVar copy-number / structural variants overlap FKRP — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →