KY

protein-coding

kyphoscoliosis peptidase

Gene summary

The protein encoded by this gene belongs to the transglutaminase-like superfamily. The protein is involved in the function, maturation and stabilization of the neuromuscular junction and may be required for normal muscle growth. Mutations in this gene are associated with myopathy, myofibrillar, 7. [provided by RefSeq, Apr 2017]

MANE transcript

NM_178554.6

Inheritance

ClinVar variants

P:10U:96B:26

Top phenotype

Myopathy, myofibrillar, 7

gnomAD constraint

pLI —, LoF o/e 0.62

Max pathogenic AF

—

Genomic locus

chr3:134,599,923-134,651,636

External References & Databases

Ensembl (ENSG00000174611)

Transcript & Mutation Effects

hg38 • Region Span ~51.7 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

kyphoscoliosis-lateral tongue atrophy-hereditary spastic paraplegia syndromeSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0044648

Submitter: Orphanet

kyphosis-lateral tongue atrophy-myofibrillar myopathy syndromeSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0044647

Submitter: Orphanet

myofibrillar myopathy 7STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014922

Submitter: PanelApp Australia

myofibrillar myopathy 7STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014922

Submitter: Labcorp Genetics (formerly Invitae)

myofibrillar myopathy 7MODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0014922

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Myopathy, myofibrillar, 7AR

Manifestation: Musculoskeletal

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 27484770; 27485408

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to KY variants in ClinVar

7 Conditions Cataloged

Inborn genetic diseasesTotal: 80

not providedTotal: 60

Myofibrillar myopathy 7Total: 24

KY-related disorderTotal: 18

not specifiedTotal: 11

KY-related disordersTotal: 1

Hereditary spastic paraplegiaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_178554.6. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	13 clinvar	3 clinvar	18
missense		1 clinvar	90 clinvar	9 clinvar	1 clinvar	101
nonsense	3 clinvar		3 clinvar			6
start loss						0
frameshift	2 clinvar	3 clinvar				5
splice donor/acceptor (+/-2bp)		1 clinvar	1 clinvar			2
Total	5	5	96	22	4	132

Highest pathogenic variant AF is 0.0000020801842

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 19 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_178554.6	RefSeq	NP_848649.3	11	MANE Select
ENST00000423778.7	Ensembl	ENSP00000397598.2	11	MANE Select
NM_001350859.2	RefSeq	NP_001337788.1	10	Standard
NM_001350860.2	RefSeq	NP_001337789.1	8	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

proteolysis

Molecular Function

peptidase activity

Cellular Component

cytoskeleton
Z disc

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000423778
Coding exons: 11
Length: 48499
Individuals with no LoFs: 124640
Homozygous LoFs: 0
Heterozygous LoFs: 64
Defined: 124704
p: 0.000257

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.826	331	376	0.880	0.0000202	4360
Missense (PolyPhen)		80	117.7	0.67969		1404
Synonymous	1.03	140	156	0.895	0.00000889	1238
Loss of Function	2.05	21	33.9	0.620	0.00000176	359

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00027	0.00026	rare
Latino/Admixed American	0.00027	0.00026	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00045	0.00044	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00027	0.00026	rare
South Asian	0.00040	0.00039	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Probable cytoskeleton-associated protease required for normal muscle growth. Involved in function, maturation and stabilization of the neuromuscular junction. May act by cleaving muscle-specific proteins such as FLNC (By similarity). {ECO:0000250}.;

Recessive Scores

pRec: 0.150

Intolerance Scores

LoFtool: 0.493
RVIS EVS: -1.2
RVIS percentile EVS: 5.83

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.223

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium