KY

Summary

KY (kyphoscoliosis peptidase, HGNC:26576) is a protein-coding gene on chromosome 3q22.2, encoding Kyphoscoliosis peptidase (Q8NBH2). Probable cytoskeleton-associated protease required for normal muscle growth.

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.

Source: NCBI Gene 339855 — RefSeq curated summary.

At a glance

• Gene–disease (curated): myofibrillar myopathy 7 (Strong, GenCC) — +2 more curated relationships
• GWAS associations: 5
• Clinical variants (ClinVar): 6 total — 1 pathogenic
• Phenotypes (HPO): 55
• MANE Select transcript: NM_178554

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26576
Approved symbol	KY
Name	kyphoscoliosis peptidase
Location	3q22.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ33207
Ensembl gene	ENSG00000174611
Ensembl biotype	protein_coding
OMIM	605739
Entrez	339855

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 4 protein_coding, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000423778, ENST00000503669, ENST00000506319, ENST00000508041, ENST00000508956, ENST00000864999

RefSeq mRNA: 5 — MANE Select: NM_178554 NM_001350859, NM_001350860, NM_001366276, NM_001366277, NM_178554

CCDS: CCDS46920, CCDS93393

Canonical transcript exons

ENST00000423778 — 11 exons

Exon	Start	End
ENSE00001184177	134608649	134608839
ENSE00001248088	134629621	134629695
ENSE00001248119	134650825	134651022
ENSE00002067229	134599923	134604474
ENSE00003497485	134627756	134627818
ENSE00003562920	134647435	134647497
ENSE00003625578	134625053	134625135
ENSE00003633094	134619148	134619265
ENSE00003639146	134620749	134620857
ENSE00003649406	134643316	134643378
ENSE00003684490	134610195	134610383

Expression profiles

Bgee: expression breadth ubiquitous, 184 present calls, max score 89.44.

FANTOM5 (CAGE): breadth broad, TPM avg 1.2907 / max 221.7441, expressed in 309 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
44714	1.2907	309

Top tissues by expression

237 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
body of tongue	UBERON:0011876	89.44	gold quality
vastus lateralis	UBERON:0001379	88.26	gold quality
quadriceps femoris	UBERON:0001377	87.84	gold quality
upper arm skin	UBERON:0004263	85.77	silver quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	85.21	gold quality
upper leg skin	UBERON:0004262	84.73	gold quality
skin of hip	UBERON:0001554	84.72	gold quality
tibia	UBERON:0000979	84.43	gold quality
Brodmann (1909) area 23	UBERON:0013554	83.50	gold quality
tongue	UBERON:0001723	82.52	gold quality
middle temporal gyrus	UBERON:0002771	82.02	gold quality
deltoid	UBERON:0001476	81.78	silver quality
biceps brachii	UBERON:0001507	81.62	gold quality
skeletal muscle tissue	UBERON:0001134	81.43	gold quality
tibialis anterior	UBERON:0001385	80.43	silver quality
muscle tissue	UBERON:0002385	79.12	gold quality
primary visual cortex	UBERON:0002436	78.32	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	78.12	gold quality
nipple	UBERON:0002030	77.43	gold quality
skin of abdomen	UBERON:0001416	77.05	gold quality
superior surface of tongue	UBERON:0007371	76.63	gold quality
penis	UBERON:0000989	76.23	gold quality
zone of skin	UBERON:0000014	75.82	gold quality
right adrenal gland cortex	UBERON:0035827	75.77	gold quality
right adrenal gland	UBERON:0001233	75.58	gold quality
hindlimb stylopod muscle	UBERON:0004252	75.24	gold quality
occipital lobe	UBERON:0002021	75.21	gold quality
skin of leg	UBERON:0001511	74.94	gold quality
pigmented layer of retina	UBERON:0001782	74.36	gold quality
pharyngeal mucosa	UBERON:0000355	74.25	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	3.88

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

144 targeting KY, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-4648	99.91	67.00	710
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-8062	99.88	68.43	995

Literature-anchored findings (GeneRIF, showing 5)

• This study shown Kyphoscoliosis peptidase (KY) mutation causes a novel congenital myopathy with core targetoid defects in two bother. (PMID:27484770)
• Homozygous c.1071delG, p.(Thr358Leufs*3) variant of KY causes neuromuscular disorder by introducing a premature stop codon. (PMID:27485408)
• KY expression is significantly downregulated in human masticatory mucosa during wound healing (PMID:28005267)
• Homozygous KY mutation was identified as a cause of progressive hereditary spastic paraplegia. High KY transcript levels were demonstrated in muscular organs and lower expression in the CNS. (PMID:28488683)
• A novel homozygous KY variant causing a complex neurological disorder. (PMID:32818658)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Ky	ENSMUSG00000035606
rattus_norvegicus	Ky	ENSRNOG00000008210
drosophila_melanogaster	Hil	FBGN0050147
caenorhabditis_elegans		WBGENE00003089

Paralogs (4): LASP1 (ENSG00000002834), NEBL (ENSG00000078114), NEB (ENSG00000183091), NRAP (ENSG00000197893)

Protein

Protein identifiers

Kyphoscoliosis peptidase — Q8NBH2 (reviewed: Q8NBH2)

All UniProt accessions (2): Q8NBH2, B4DGA7

UniProt curated annotations — full annotation on UniProt →

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.

Subunit / interactions. Interacts with IGFN1 and FLNC.

Subcellular location. Cytoplasm. Cytoskeleton. Myofibril. Sarcomere. Z line.

Tissue specificity. Highly expressed in skeletal muscle.

Disease relevance. Myopathy, myofibrillar, 7 (MFM7) [MIM:617114] A form of myofibrillar myopathy, a group of chronic neuromuscular disorders characterized at ultrastructural level by disintegration of the sarcomeric Z disk and myofibrils, and replacement of the normal myofibrillar markings by small dense granules, or larger hyaline masses, or amorphous material. MFM7 is an autosomal recessive form, clinically characterized by early childhood onset of slowly progressive muscle weakness and mild atrophy primarily affecting the lower limbs, associated with joint contractures. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the transglutaminase-like superfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8NBH2-4	4	yes
Q8NBH2-3	3

RefSeq proteins (5): NP_001337788, NP_001337789, NP_001353205, NP_001353206, NP_848649* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002931	Transglutaminase-like	Domain
IPR038765	Papain-like_cys_pep_sf	Homologous_superfamily
IPR052557	CAP/Cytokinesis_protein	Family
IPR056564	Ig-like_KY	Domain

Pfam: PF01841, PF23265

UniProt features (9 total): active site 3, region of interest 2, chain 1, compositionally biased region 1, splice variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NBH2-F1	80.04	0.61

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (3): 225; 267; 282

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 222 (showing top): GOBP_NEUROMUSCULAR_JUNCTION_DEVELOPMENT, CREL_01, FREAC2_01, BENPORATH_ES_WITH_H3K27ME3, MEF2_02, FOXO4_01, TCF4_Q5, GOBP_CELL_JUNCTION_ORGANIZATION, GOBP_MUSCLE_STRUCTURE_DEVELOPMENT, GGGNNTTTCC_NFKB_Q6_01, TGANTCA_AP1_C, chr3q22, BREDEMEYER_RAG_SIGNALING_NOT_VIA_ATM_UP, MEF2_Q6_01, CTAWWWATA_RSRFC4_Q2

GO Biological Process (3): proteolysis (GO:0006508), muscle organ development (GO:0007517), neuromuscular junction development (GO:0007528)

GO Molecular Function (2): peptidase activity (GO:0008233), hydrolase activity (GO:0016787)

GO Cellular Component (3): cytoplasm (GO:0005737), cytoskeleton (GO:0005856), Z disc (GO:0030018)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
protein metabolic process	1
animal organ development	1
muscle structure development	1
synapse organization	1
hydrolase activity	1
catalytic activity, acting on a protein	1
catalytic activity	1
intracellular anatomical structure	1
intracellular membraneless organelle	1
I band	1

Protein interactions and networks

STRING

900 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KY	MYBPC1	Q00872	771
KY	FLNC	Q14315	719
KY	GPN2	Q9H9Y4	523
KY	BLMH	Q13867	455
KY	TTN	Q8WZ42	451
KY	TRIM72	Q6ZMU5	416
KY	MSS51	Q4VC12	414
KY	ACY1	Q03154	407
KY	H8Y6P7	H8Y6P7	397
KY	SPSB3	Q6PJ21	386
KY	OSGEP	Q9NPF4	372
KY	ANKRD29	Q8N6D5	371
KY	PGPEP1	Q9NXJ5	370
KY	METAP1	P53582	361
KY	SDK1	Q7Z5N4	357

IntAct

0 interactions, top by confidence:

BioGRID (2): KY (Affinity Capture-MS), ALDOA (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A0AVI2, A0FGR9, A3KGK3, A6NCM1, A6QQP7, B0DOB4, B3DLH6, B7FF09, B7ZC32, D3ZGS3, F1S5L4, O00329, O35904, O70145, O75923, P0DM40, P32019, P58069, P97564, Q0VA04, Q15283, Q17I16, Q1LXZ7, Q2WGJ9, Q32PH0, Q5DTI8, Q5GJ77, Q5RE88, Q5T0N1, Q5XIZ9, Q61586, Q62240, Q63713, Q69ZN7, Q6DCF6, Q6P5U7, Q6PA97, Q86VS3, Q86YR7, Q8BWR4

Diamond homologs: Q8C8H8, Q8NBH2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

6 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	0
Likely benign	1
Benign	3

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
254182	NM_178554.6(KY):c.1071del (p.Thr358fs)	Pathogenic

SpliceAI

1984 predictions. Top by Δscore:

Variant	Effect	Δscore
3:134619142:TCGTA:T	donor_loss	1.0000
3:134619143:CGTA:C	donor_loss	1.0000
3:134619144:GTAC:G	donor_loss	1.0000
3:134619145:TA:T	donor_loss	1.0000
3:134619147:C:CT	donor_loss	1.0000
3:134619262:TACT:T	acceptor_gain	1.0000
3:134619264:CT:C	acceptor_gain	1.0000
3:134619266:C:CC	acceptor_gain	1.0000
3:134620743:GCCTA:G	donor_loss	1.0000
3:134620744:CCTA:C	donor_loss	1.0000
3:134620745:CTA:C	donor_loss	1.0000
3:134620746:TACCT:T	donor_loss	1.0000
3:134620747:ACCTA:A	donor_loss	1.0000
3:134629619:A:AC	donor_gain	1.0000
3:134629620:C:CC	donor_gain	1.0000
3:134629694:CC:C	acceptor_gain	1.0000
3:134629695:CC:C	acceptor_gain	1.0000
3:134629696:C:CC	acceptor_gain	1.0000
3:134650826:T:TA	donor_gain	1.0000
3:134650877:AC:A	donor_gain	1.0000
3:134650878:CC:C	donor_gain	1.0000
3:134604471:TTCA:T	acceptor_gain	0.9900
3:134604472:TCA:T	acceptor_gain	0.9900
3:134604473:CA:C	acceptor_gain	0.9900
3:134604473:CAC:C	acceptor_gain	0.9900
3:134604475:C:CC	acceptor_gain	0.9900
3:134608643:GCTCA:G	donor_loss	0.9900
3:134608644:CTCA:C	donor_loss	0.9900
3:134608645:TCA:T	donor_loss	0.9900
3:134608646:CA:C	donor_loss	0.9900

AlphaMissense

4393 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:134608731:A:C	F336L	0.999
3:134608731:A:T	F336L	0.999
3:134608733:A:G	F336L	0.999
3:134608790:G:C	H317D	0.999
3:134610262:A:G	W278R	0.999
3:134610262:A:T	W278R	0.999
3:134610289:A:G	W269R	0.999
3:134610289:A:T	W269R	0.999
3:134610341:C:A	K251N	0.999
3:134610341:C:G	K251N	0.999
3:134610351:C:T	G248D	0.999
3:134603604:A:G	L654P	0.998
3:134608788:G:C	H317Q	0.998
3:134608788:G:T	H317Q	0.998
3:134608789:T:G	H317P	0.998
3:134608827:G:C	F304L	0.998
3:134608827:G:T	F304L	0.998
3:134608829:A:G	F304L	0.998
3:134610203:G:C	F297L	0.998
3:134610203:G:T	F297L	0.998
3:134610205:A:G	F297L	0.998
3:134610238:C:G	G286R	0.998
3:134610241:A:G	W285R	0.998
3:134610241:A:T	W285R	0.998
3:134610250:C:G	D282H	0.998
3:134610287:C:A	W269C	0.998
3:134610287:C:G	W269C	0.998
3:134610351:C:A	G248V	0.998
3:134610352:C:G	G248R	0.998
3:134620767:A:G	W192R	0.998

dbSNP variants (sampled 300 via entrez): RS1000055320 (3:134642182 C>T), RS1000149804 (3:134632827 A>G), RS1000178393 (3:134626279 G>A), RS1000209422 (3:134639218 T>C), RS1000270016 (3:134639788 A>C,G), RS1000288432 (3:134601293 A>G), RS1000340228 (3:134601624 G>A), RS1000434378 (3:134645602 C>T), RS1000446874 (3:134641976 A>C,G), RS1000507354 (3:134606058 C>T), RS1000542634 (3:134651696 C>G,T), RS1000558167 (3:134607273 G>A), RS1000602002 (3:134648121 C>G,T), RS1000680995 (3:134613033 G>A,T), RS1000734658 (3:134613345 A>T)

Disease associations

OMIM: gene MIM:605739 | disease phenotypes: MIM:617114

GenCC curated gene-disease

Disease	Classification	Inheritance
myofibrillar myopathy 7	Strong	Autosomal recessive
kyphosis-lateral tongue atrophy-myofibrillar myopathy syndrome	Supportive	Autosomal recessive
kyphoscoliosis-lateral tongue atrophy-hereditary spastic paraplegia syndrome	Supportive	Autosomal recessive

Mondo (3): myofibrillar myopathy 7 (MONDO:0014922), kyphosis-lateral tongue atrophy-myofibrillar myopathy syndrome (MONDO:0044647), kyphoscoliosis-lateral tongue atrophy-hereditary spastic paraplegia syndrome (MONDO:0044648)

Orphanet (0):

HPO phenotypes

55 total (30 of 55 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000020	Urinary incontinence
HP:0000708	Atypical behavior
HP:0001249	Intellectual disability
HP:0001263	Global developmental delay
HP:0001265	Hyporeflexia
HP:0001272	Cerebellar atrophy
HP:0001288	Gait disturbance
HP:0001324	Muscle weakness
HP:0001371	Flexion contracture
HP:0001761	Pes cavus
HP:0001762	Talipes equinovarus
HP:0001771	Achilles tendon contracture
HP:0002015	Dysphagia
HP:0002059	Cerebral atrophy
HP:0002061	Lower limb spasticity
HP:0002194	Delayed gross motor development
HP:0002395	Lower limb hyperreflexia
HP:0002607	Bowel incontinence
HP:0002650	Scoliosis
HP:0002751	Kyphoscoliosis
HP:0002828	Multiple joint contractures
HP:0002938	Lumbar hyperlordosis
HP:0002942	Thoracic kyphosis
HP:0002987	Elbow flexion contracture
HP:0003044	Shoulder flexion contracture
HP:0003093	Limited hip extension
HP:0003202	Skeletal muscle atrophy
HP:0003236	Elevated circulating creatine kinase concentration
HP:0003306	Spinal rigidity

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST004407_7	Neurocognitive impairment in HIV-1 infection (dichotomous)	6.000000e-06
GCST012226_634	Waist circumference adjusted for body mass index	1.000000e-10
GCST012226_635	Waist circumference adjusted for body mass index	5.000000e-12
GCST012231_190	A body shape index	3.000000e-11
GCST90000025_951	Appendicular lean mass	5.000000e-21

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007998	cognitive impairment measurement
EFO:0007789	BMI-adjusted waist circumference
EFO:0004980	appendicular lean mass

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

14 total (human), top 14 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
triphenyl phosphate	affects expression	1
di-n-butylphosphoric acid	affects expression	1
abrine	decreases expression	1
bisphenol S	increases methylation	1
(+)-JQ1 compound	decreases expression	1
Fulvestrant	increases methylation	1
Acetaminophen	increases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Doxorubicin	decreases expression	1
Nickel	decreases expression	1
Smoke	increases expression	1
Aflatoxin B1	decreases methylation	1
Antirheumatic Agents	decreases expression	1
Cadmium Chloride	increases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.