KRTCAP3

Summary

KRTCAP3 (keratinocyte associated protein 3, HGNC:28943) is a protein-coding gene on chromosome 2p23.3, encoding Keratinocyte-associated protein 3 (Q53RY4).

Predicted to be located in membrane.

Source: NCBI Gene 200634 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 88 total — 1 pathogenic
• Phenotypes (HPO): 1
• MANE Select transcript: NM_173853

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28943
Approved symbol	KRTCAP3
Name	keratinocyte associated protein 3
Location	2p23.3
Locus type	gene with protein product
Status	Approved
Aliases	KCP3
Ensembl gene	ENSG00000157992
Ensembl biotype	protein_coding
OMIM	619261
Entrez	200634

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 14 protein_coding, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000288873, ENST00000407293, ENST00000452499, ENST00000453171, ENST00000464699, ENST00000494572, ENST00000543753, ENST00000872248, ENST00000872249, ENST00000872250, ENST00000872251, ENST00000872252, ENST00000872253, ENST00000872254, ENST00000914468, ENST00000914469

RefSeq mRNA: 3 — MANE Select: NM_173853 NM_001168364, NM_001321325, NM_173853

CCDS: CCDS1754

Canonical transcript exons

ENST00000288873 — 7 exons

Exon	Start	End
ENSE00001036353	27442579	27442763
ENSE00001300891	27442381	27442440
ENSE00001334119	27444186	27444297
ENSE00003492678	27443949	27444061
ENSE00003634903	27443398	27443532
ENSE00003660141	27442842	27442901
ENSE00003667512	27443074	27443280

Expression profiles

Bgee: expression breadth ubiquitous, 197 present calls, max score 97.82.

FANTOM5 (CAGE): breadth broad, TPM avg 2.6651 / max 123.8729, expressed in 456 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
19372	1.9660	402
19373	0.5390	251
19371	0.1601	68

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of transverse colon	UBERON:0004991	97.82	gold quality
pancreatic ductal cell	CL:0002079	96.53	gold quality
right uterine tube	UBERON:0001302	96.35	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	95.62	gold quality
body of pancreas	UBERON:0001150	95.36	gold quality
rectum	UBERON:0001052	94.77	gold quality
minor salivary gland	UBERON:0001830	94.08	gold quality
lower esophagus mucosa	UBERON:0035834	92.83	gold quality
ileal mucosa	UBERON:0000331	92.61	gold quality
pancreas	UBERON:0001264	92.54	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	92.06	gold quality
saliva-secreting gland	UBERON:0001044	91.94	gold quality
transverse colon	UBERON:0001157	91.25	gold quality
islet of Langerhans	UBERON:0000006	91.24	gold quality
mouth mucosa	UBERON:0003729	90.76	gold quality
body of stomach	UBERON:0001161	90.52	gold quality
adenohypophysis	UBERON:0002196	90.33	gold quality
esophagus mucosa	UBERON:0002469	89.90	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	89.71	gold quality
small intestine Peyer’s patch	UBERON:0003454	89.71	gold quality
duodenum	UBERON:0002114	89.63	gold quality
colonic mucosa	UBERON:0000317	89.21	gold quality
mucosa of sigmoid colon	UBERON:0004993	88.95	gold quality
pituitary gland	UBERON:0000007	88.94	gold quality
prostate gland	UBERON:0002367	88.82	gold quality
small intestine	UBERON:0002108	88.34	gold quality
left lobe of thyroid gland	UBERON:0001120	88.01	gold quality
right lobe of thyroid gland	UBERON:0001119	87.82	gold quality
stomach	UBERON:0000945	87.73	gold quality
nasal cavity mucosa	UBERON:0001826	87.36	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-8410	yes	45.04
E-MTAB-6524	no	103.24
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

6 targeting KRTCAP3, 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-4668-5P	99.79	70.58	3782
HSA-MIR-556-3P	99.74	68.75	1203
HSA-MIR-6870-3P	98.08	65.10	692
HSA-MIR-4727-3P	96.75	64.97	415
HSA-MIR-3169	96.40	67.58	698
HSA-MIR-3117-3P	95.96	67.82	473

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio		ENSDARG00000090072
mus_musculus	Krtcap3	ENSMUSG00000029149
rattus_norvegicus	Krtcap3	ENSRNOG00000047941

Paralogs (1): TMEM54 (ENSG00000121900)

Protein

Protein identifiers

Keratinocyte-associated protein 3 — Q53RY4 (reviewed: Q53RY4)

All UniProt accessions (4): Q53RY4, A0A669KBF3, F8WDP6, H7BZ70

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Membrane.

Tissue specificity. Expressed in skin, pancreas and keratinocytes.

Similarity. Belongs to the TMEM54 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q53RY4-1	1	yes
Q53RY4-2	2

RefSeq proteins (3): NP_001161836, NP_001308254, NP_776252* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR020977	Beta-casein-like	Family

Pfam: PF12304

UniProt features (7 total): transmembrane region 4, chain 1, splice variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q53RY4-F1	76.17	0.28

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 52 (showing top): WAMUNYOKOLI_OVARIAN_CANCER_LMP_UP, FIGUEROA_AML_METHYLATION_CLUSTER_3_UP, CHYLA_CBFA2T3_TARGETS_DN, ID2_TARGET_GENES, MAFG_TARGET_GENES, SETD7_TARGET_GENES, SNRNP70_TARGET_GENES, MIR4704_3P, MIR6840_3P, chr2p23, MIR4727_3P, MIR604, GSE17580_TREG_VS_TEFF_UP, GSE17721_LPS_VS_PAM3CSK4_2H_BMDC_DN, MURARO_PANCREAS_DUCTAL_CELL

GO Biological Process (0):

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (1): membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

598 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KRTCAP3	CCDC121	Q6ZUS5	654
KRTCAP3	ZNF512	Q96ME7	605
KRTCAP3	NRBP1	Q9UHY1	587
KRTCAP3	TTC22	Q5TAA0	572
KRTCAP3	FNDC4	Q9H6D8	565
KRTCAP3	ZNF888	P0CJ79	527
KRTCAP3	ZNF513	Q8N8E2	523
KRTCAP3	SPATC1L	Q9H0A9	511
KRTCAP3	TSPEAR	Q8WU66	504
KRTCAP3	GTF3C2	Q8WUA4	474
KRTCAP3	PM20D1	Q6GTS8	461
KRTCAP3	KRT82	Q9NSB4	457
KRTCAP3	SEPTIN8	Q92599	456
KRTCAP3	SPATA31H1	Q68DN1	447
KRTCAP3	ZNF490	Q9ULM2	444

IntAct

8 interactions, top by confidence:

A	B	Type	Score
KRTCAP3	MEOX2	psi-mi:“MI:0915”(physical association)	0.560
KRTCAP3	FNDC9	psi-mi:“MI:0915”(physical association)	0.560
KRTCAP3	SLC22A23	psi-mi:“MI:0914”(association)	0.350
KRTCAP3	MEOX2	psi-mi:“MI:0915”(physical association)	0.000
KRTCAP3	FNDC9	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (33): KRTCAP3 (PCA), KRTCAP3 (Two-hybrid), FNDC9 (Two-hybrid), VAMP3 (Affinity Capture-MS), ATP6V0A2 (Affinity Capture-MS), KLRG2 (Affinity Capture-MS), WDR41 (Affinity Capture-MS), CD47 (Affinity Capture-MS), KIAA2013 (Affinity Capture-MS), TMEM186 (Affinity Capture-MS), GOLPH3 (Affinity Capture-MS), LPHN3 (Affinity Capture-MS), REEP5 (Affinity Capture-MS), SMCR8 (Affinity Capture-MS), SLC22A23 (Affinity Capture-MS)

ESM2 similar proteins: A0PJX8, A4IFG4, A5D7M7, A6NKF7, A7MBM2, E9PY61, J3QMI4, L5KLU7, O70491, Q03395, Q08E36, Q0V8E7, Q0VD38, Q1KZG0, Q2KJ98, Q3SWY4, Q3TYP4, Q49LS1, Q4QR83, Q53RY4, Q5GH56, Q5GH64, Q5GH72, Q5R7B4, Q5T1A1, Q5XK03, Q66K66, Q674R7, Q6EBV9, Q6GQT5, Q6P5W5, Q6PEY1, Q6PRD1, Q80WF4, Q80ZU9, Q86XJ0, Q8BG75, Q8K177, Q8N144, Q8N4L1

Diamond homologs: Q3SZ72, Q3ZCD2, Q494T4, Q497B3, Q53RY4, Q8K177, Q969K7, Q9D7S1

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	57
Likely benign	13
Benign	1

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
191368	NM_015662.3(IFT172):c.4815T>G (p.Asp1605Glu)	Pathogenic

SpliceAI

1725 predictions. Top by Δscore:

Variant	Effect	Δscore
2:27445102:TATCC:T	acceptor_loss	1.0000
2:27445103:ATCC:A	acceptor_loss	1.0000
2:27445104:TC:T	acceptor_gain	1.0000
2:27445104:TCC:T	acceptor_loss	1.0000
2:27445105:CC:C	acceptor_gain	1.0000
2:27445105:CCTGT:C	acceptor_loss	1.0000
2:27445106:C:CC	acceptor_gain	1.0000
2:27445106:CT:C	acceptor_loss	1.0000
2:27445107:T:A	acceptor_loss	1.0000
2:27445293:TA:T	donor_loss	1.0000
2:27445445:GCCTC:G	acceptor_gain	1.0000
2:27445446:CCTCC:C	acceptor_gain	1.0000
2:27445447:CTC:C	acceptor_gain	1.0000
2:27445448:TC:T	acceptor_gain	1.0000
2:27445449:CC:C	acceptor_gain	1.0000
2:27445449:CCTGG:C	acceptor_loss	1.0000
2:27445450:C:CC	acceptor_gain	1.0000
2:27445450:C:T	acceptor_gain	1.0000
2:27445919:C:A	donor_gain	1.0000
2:27445923:A:AC	donor_gain	1.0000
2:27445923:ACT:A	donor_loss	1.0000
2:27445924:C:CC	donor_gain	1.0000
2:27445924:CTC:C	donor_loss	1.0000
2:27445925:TCA:T	donor_loss	1.0000
2:27445926:CA:C	donor_loss	1.0000
2:27445927:A:AC	donor_gain	1.0000
2:27445927:AC:A	donor_loss	1.0000
2:27445928:C:CC	donor_gain	1.0000
2:27442441:G:GG	donor_gain	0.9900
2:27442718:G:GT	donor_gain	0.9900

AlphaMissense

1502 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:27443416:T:A	W167R	0.988
2:27443416:T:C	W167R	0.988
2:27443260:T:C	F154L	0.987
2:27443262:T:A	F154L	0.987
2:27443262:T:G	F154L	0.987
2:27442736:T:A	N62K	0.984
2:27442736:T:G	N62K	0.984
2:27442842:A:C	S72R	0.984
2:27442844:C:A	S72R	0.984
2:27442844:C:G	S72R	0.984
2:27443261:T:G	F154C	0.980
2:27442854:G:A	G76R	0.976
2:27442854:G:C	G76R	0.976
2:27443106:C:A	N102K	0.976
2:27443106:C:G	N102K	0.976
2:27442635:G:C	G29R	0.971
2:27442636:G:A	G29D	0.970
2:27442855:G:A	G76E	0.969
2:27443418:G:C	W167C	0.969
2:27443418:G:T	W167C	0.969
2:27442615:G:A	G22D	0.965
2:27442723:A:G	Y58C	0.964
2:27442755:G:A	G69R	0.963
2:27442755:G:C	G69R	0.963
2:27443276:T:C	I159T	0.963
2:27442722:T:C	Y58H	0.961
2:27442614:G:C	G22R	0.959
2:27443134:G:C	G112R	0.959
2:27443183:T:A	L128H	0.959
2:27442671:G:C	G41R	0.958

dbSNP variants (sampled 300 via entrez): RS1000116662 (2:27440521 G>A), RS1000130365 (2:27443083 C>G,T), RS1000610224 (2:27445518 G>A,C), RS1001677984 (2:27442956 G>A,C), RS1002532716 (2:27442746 G>C), RS1002563888 (2:27442503 G>A,C,T), RS1003536519 (2:27441770 G>C,T), RS1003556173 (2:27441443 G>A), RS1004434029 (2:27443789 T>G), RS1004592347 (2:27442782 C>A,T), RS1005562998 (2:27441975 C>T), RS1006442735 (2:27441502 C>T), RS1006792481 (2:27446576 C>G), RS1006823501 (2:27446196 G>A,C), RS1006996521 (2:27442450 G>A)

Disease associations

OMIM: gene MIM:619261 | disease phenotypes: MIM:615630, MIM:616394, MIM:619471

GenCC curated gene-disease

Mondo (4): short-rib thoracic dysplasia 10 with or without polydactyly (MONDO:0014284), retinitis pigmentosa 71 (MONDO:0014618), Bardet-Biedl syndrome 20 (MONDO:0023670), inherited retinal dystrophy (MONDO:0019118)

Orphanet (3): Jeune syndrome (Orphanet:474), Retinitis pigmentosa (Orphanet:791), OBSOLETE: Inherited retinal disorder (Orphanet:71862)

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0000556	Retinal dystrophy

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST001905_4	Hypertriglyceridemia	2.000000e-13
GCST004131_72	Inflammatory bowel disease	1.000000e-07
GCST004132_64	Crohn’s disease	6.000000e-11

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004530	triglyceride measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D058499	Retinal Dystrophies	C11.768.585.658

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression	3
Cadmium Chloride	decreases expression, increases abundance	2
aristolochic acid I	increases expression	1
triphenyl phosphate	affects expression	1
sodium arsenite	decreases expression	1
butyraldehyde	decreases expression	1
pentanal	decreases expression	1
abrine	increases expression	1
jinfukang	increases expression	1
Ethanol	affects cotreatment, increases abundance, increases expression	1
Vehicle Emissions	increases methylation	1
Cadmium	decreases expression, increases abundance	1
Calcitriol	increases expression	1
Carbamazepine	affects expression	1
Diethylhexyl Phthalate	increases expression	1
Gasoline	affects cotreatment, increases abundance, increases expression	1
Polychlorinated Biphenyls	affects expression	1
Polycyclic Aromatic Hydrocarbons	increases expression, affects cotreatment, increases abundance	1
Progesterone	decreases expression	1
Cyclosporine	decreases expression	1
Aflatoxin B1	decreases expression	1
Okadaic Acid	decreases expression	1
Particulate Matter	affects cotreatment, increases abundance, increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04224207	PHASE3	COMPLETED	Management of Retinitis Pigmentosa by Mesenchymal Stem Cells by Wharton’s Jelly Derived Mesenchymal Stem Cells
NCT07082855	PHASE3	NOT_YET_RECRUITING	A Multicenter, Randomized, Double-Blind, Controlled Clinical Study of Minocycline for the Treatment of Retinitis Pigmentosa
NCT03763227	PHASE2	COMPLETED	Intravitreal Ranibizumab (Lucentis®) in the Treatment of Non-leaking Macular Cysts in Retinal Dystrophy
NCT04068207	PHASE2	COMPLETED	Minocycline Treatment in Retinitis Pigmentosa
NCT04945772	PHASE2	COMPLETED	Efficacy and Safety of MCO-010 Optogenetic Therapy in Adults With Retinitis Pigmentosa [RESTORE]
NCT05902962	PHASE1	COMPLETED	SAD of IVT VP-001 in PRPF31 Mutation-Associated Retinal Dystrophy Subjects
NCT06319872	PHASE1	RECRUITING	The Effects of Disulfiram (Antabuse®) on Visual Acuity in Patients With Retinal Degeneration
NCT06455826	PHASE1	COMPLETED	MAD of IVT VP-001 in PRPF31 Mutation-Associated Retinal Dystrophy Subjects (Wallaby)
NCT04855045	PHASE2/PHASE3	UNKNOWN	An Open-label, Dose Escalation and Double-masked, Randomized, Controlled Trial Evaluating Safety and Tolerability of Sepofarsen in Children (<8 Years of Age) With LCA10 Caused by Mutations in the CEP290 Gene.
NCT03872479	PHASE1/PHASE2	UNKNOWN	Single Ascending Dose Study in Participants With LCA10
NCT04123626	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	A Study to Evaluate the Safety and Tolerability of QR-1123 in Subjects With Autosomal Dominant Retinitis Pigmentosa Due to the P23H Mutation in the RHO Gene
NCT04545736	PHASE1/PHASE2	RECRUITING	Oral Metformin for Treatment of ABCA4 Retinopathy
NCT06212297	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Fellow-eye Study (FE) of LX101 in Subjects With Inherited Retinal Dystrophy
NCT06852963	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	A Repeat-Dose, Open-Label, Two Arm Safety and Efficacy Study of Two Doses of VP-001 Administered Intravitreally in Participants With Confirmed PRPF31 Mutation-Associated Retinal Dystrophy, Including Participants Previously Treated With VP001
NCT07177196	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Personalized Antisense Oligonucleotide Therapy for a Single Participant With PRPH2 Mutation Associated With Retinal Dystrophy
NCT07063030	EARLY_PHASE1	RECRUITING	A Study of LX107 Gene Therapy in AIPL1-IRD Patients
NCT01546181	Not specified	COMPLETED	Retinal Imaging by Adaptive Optics in Healthy Eyes and During Retinal and General Diseases
NCT01876147	Not specified	COMPLETED	Visual and Functional Assessment in Low Vision Patients
NCT01920867	Not specified	UNKNOWN	Stem Cell Ophthalmology Treatment Study
NCT02014389	Not specified	RECRUITING	Evaluation of Objective Perimetry Using Chromatic Multifocal Pupillometer
NCT02983305	Not specified	COMPLETED	Optical Head-Mounted Display Technology for Low Vision Rehabilitation
NCT03592017	Not specified	COMPLETED	Performance of Long-wavelength Autofluorescence Imaging
NCT03662386	Not specified	TERMINATED	Prospective Analysis of Genotype-phenotype Correlations Observed in a Large Cohort of Patients With Hereditary Retinal Dystrophies - GEPHIRD
NCT03691168	Not specified	UNKNOWN	Multi-center Observation of the Natural Course of Inherited Retinal Dystrophies
NCT03843840	Not specified	COMPLETED	Dual Wavelength OCT
NCT03853252	Not specified	COMPLETED	iPS Cells of Patients for Models of Retinal Dystrophies
NCT05130385	Not specified	UNKNOWN	High Resolution Optical Coherence Tomography
NCT05294978	Not specified	RECRUITING	EyeConic: Qualification for Cone-Optogenetics
NCT05573984	Not specified	ACTIVE_NOT_RECRUITING	Natural History of PRPF31 Mutation-Associated Retinal Dystrophy
NCT05793515	Not specified	COMPLETED	Mechanisms of Inherited Retinal Dystrophies Using Whole Genome Sequencing and in Vitro and in Vivo Models
NCT05820100	Not specified	COMPLETED	Observational Study to Assess the Reliability and Validity of the MLYMT and MLSDT
NCT05976139	Not specified	RECRUITING	Micropulsed Laser in Patients With Macular Oedema in Retinal Dystrophies
NCT06162585	Not specified	ACTIVE_NOT_RECRUITING	Non-Interventional Long Term Follow-up Study of Participants Previously Enrolled in the RESTORE Study
NCT06177977	Not specified	RECRUITING	SS-HH-OCT as a Novel Diagnostic Modality for Early-Onset Retinal Dystrophies (EORDs)
NCT06375239	Not specified	RECRUITING	Observational Study to Assess Endpoint Operational Feasibility & Measurement Properties in Patients with Retinal Degeneration
NCT06908161	Not specified	NOT_YET_RECRUITING	Functional Assessments in Vision Impairment
NCT07085533	Not specified	RECRUITING	Natural History Study of Inherited Retinal Diseases
NCT07502664	Not specified	RECRUITING	Development and Evaluation of Functional Visual Field and Navigation Endpoints in Moderate to Profound Inherited Retinal Disease (DEFINE-IRD)
NCT07529041	Not specified	ENROLLING_BY_INVITATION	Real-time Acoustic Biofeedback for Enhancing Fixation Stability: A Proof-of-concept Study to Improve Ophthalmic Imaging Diagnostic Quality