KRTDAP

Summary

KRTDAP (keratinocyte differentiation associated protein, HGNC:16313) is a protein-coding gene on chromosome 19q13.12, encoding Keratinocyte differentiation-associated protein (P60985). May act as a soluble regulator of keratinocyte differentiation.

This gene encodes a protein which may function in the regulation of keratinocyte differentiation and maintenance of stratified epithelia. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 388533 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 19 total
• MANE Select transcript: NM_207392

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16313
Approved symbol	KRTDAP
Name	keratinocyte differentiation associated protein
Location	19q13.12
Locus type	gene with protein product
Status	Approved
Aliases	KDAP, UNQ467
Ensembl gene	ENSG00000188508
Ensembl biotype	protein_coding
OMIM	617212
Entrez	388533

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000338897, ENST00000479340, ENST00000484218

RefSeq mRNA: 2 — MANE Select: NM_207392 NM_001244847, NM_207392

CCDS: CCDS12462, CCDS59377

Canonical transcript exons

ENST00000338897 — 6 exons

Exon	Start	End
ENSE00003491127	35487324	35487466
ENSE00003532514	35487712	35487759
ENSE00003539564	35488662	35488703
ENSE00003545032	35488802	35488840
ENSE00003595212	35488441	35488485
ENSE00003845287	35490356	35490464

Expression profiles

Bgee: expression breadth ubiquitous, 165 present calls, max score 99.94.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 12.3092 / max 6335.1726, expressed in 69 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
180523	12.3092	69

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
penis	UBERON:0000989	99.94	gold quality
upper leg skin	UBERON:0004262	99.94	gold quality
mammalian vulva	UBERON:0000997	99.93	gold quality
upper arm skin	UBERON:0004263	99.93	gold quality
nipple	UBERON:0002030	99.90	gold quality
skin of hip	UBERON:0001554	99.87	gold quality
gingival epithelium	UBERON:0001949	99.83	gold quality
gingiva	UBERON:0001828	99.82	gold quality
skin of abdomen	UBERON:0001416	99.74	gold quality
zone of skin	UBERON:0000014	99.54	gold quality
skin of leg	UBERON:0001511	99.44	gold quality
lower esophagus mucosa	UBERON:0035834	96.87	gold quality
body of tongue	UBERON:0011876	95.09	gold quality
oral cavity	UBERON:0000167	91.96	gold quality
esophagus mucosa	UBERON:0002469	89.34	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	89.31	gold quality
vagina	UBERON:0000996	88.75	gold quality
tongue	UBERON:0001723	87.86	gold quality
left testis	UBERON:0004533	83.42	gold quality
right testis	UBERON:0004534	83.42	gold quality
sperm	CL:0000019	80.88	gold quality
testis	UBERON:0000473	80.45	gold quality
esophagus squamous epithelium	UBERON:0006920	80.40	gold quality
mouth mucosa	UBERON:0003729	79.25	gold quality
esophagus	UBERON:0001043	79.02	gold quality
minor salivary gland	UBERON:0001830	76.31	gold quality
superior surface of tongue	UBERON:0007371	75.93	gold quality
right lobe of thyroid gland	UBERON:0001119	75.57	gold quality
gastrocnemius	UBERON:0001388	75.38	gold quality
right lung	UBERON:0002167	74.98	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-8142	yes	26994.58
E-ANND-3	yes	25.40
E-MTAB-10596	no	1129.14

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

11 targeting KRTDAP, 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-432-3P	100.00	67.86	705
HSA-MIR-1193	100.00	65.93	529
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-1200	99.71	70.42	1838
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-940	99.37	66.14	2064
HSA-MIR-6808-5P	99.31	66.23	2150
HSA-MIR-6893-5P	99.31	66.25	2119
HSA-MIR-544B	99.18	67.41	1632

Literature-anchored findings (GeneRIF, showing 1)

• Kdap may serve as a soluble regulator of keratinocyte differentiation. (PMID:15140226)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Krtdap	ENSMUSG00000074199
rattus_norvegicus	Krtdap	ENSRNOG00000062262

Protein

Protein identifiers

Keratinocyte differentiation-associated protein — P60985 (reviewed: P60985)

All UniProt accessions (1): P60985

UniProt curated annotations — full annotation on UniProt →

Function. May act as a soluble regulator of keratinocyte differentiation. May play an important role in embryonic skin morphogenesis.

Subcellular location. Secreted.

Tissue specificity. Highly expressed in skin and detected at lower levels in thymus. In skin, found exclusively in lamellar granules of granular keratinocytes and in the intracellular space of the stratum corneum. Also highly expressed in oral mucosa, tongue, esophagus, and stomach, and at much lower levels in bladder and uterus. Not detected in gastrointestinal mucosa.

Induction. Up-regulated in situ in psoriatic skin (at protein level).

Isoforms (2)

UniProt ID	Names	Canonical?
P60985-1	1	yes
P60985-2	2

RefSeq proteins (2): NP_001231776, NP_997275* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR028196	KRTDAP	Family

Pfam: PF15200

UniProt features (3 total): signal peptide 1, chain 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P60985-F1	59.64	0.00

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-9725554	Differentiation of Keratinocytes in Interfollicular Epidermis in Mammalian Skin
R-HSA-1266738	Developmental Biology
R-HSA-9734767	Developmental Cell Lineages

MSigDB gene sets: 66 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_DN, GOCC_SECRETORY_GRANULE, MARTINEZ_RB1_TARGETS_UP, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_DN, GOBP_EPIDERMIS_DEVELOPMENT, MARTINEZ_RB1_AND_TP53_TARGETS_UP, RICKMAN_HEAD_AND_NECK_CANCER_C, GOCC_SECRETORY_VESICLE, GOCC_LAMELLAR_BODY, PYEON_HPV_POSITIVE_TUMORS_DN, RAY_TUMORIGENESIS_BY_ERBB2_CDC25A_UP, MIKKELSEN_MCV6_LCP_WITH_H3K4ME3, YAO_TEMPORAL_RESPONSE_TO_PROGESTERONE_CLUSTER_2, LEE_BMP2_TARGETS_DN, FORTSCHEGGER_PHF8_TARGETS_UP

GO Biological Process (2): epidermis development (GO:0008544), cell differentiation (GO:0030154)

GO Molecular Function (0):

GO Cellular Component (3): obsolete extracellular space (GO:0005615), lamellar body (GO:0042599), extracellular region (GO:0005576)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Developmental Cell Lineages of the Integumentary System	1
Developmental Biology	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
tissue development	1
cellular developmental process	1
secretory granule	1
cellular anatomical structure	1

Protein interactions and networks

STRING

626 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KRTDAP	SBSN	Q6UWP8	790
KRTDAP	CNFN	Q9BYD5	668
KRTDAP	DMKN	Q6E0U4	620
KRTDAP	TGM3	Q08188	582
KRTDAP	CRNN	Q9UBG3	516
KRTDAP	KRT10	P13645	513
KRTDAP	KRT80	Q6KB66	513
KRTDAP	LGALS7B	P47929	509
KRTDAP	CDSN	Q15517	509
KRTDAP	KRT2	P35908	496
KRTDAP	SCEL	O95171	484
KRTDAP	KRT1	P04264	480
KRTDAP	KRT77	Q7Z794	473
KRTDAP	CXorf49C	A0A1B0GWI6	446
KRTDAP	SPINK7	P58062	420

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: A0A0D1E6R6, A0A0D1EAR7, A0A172M476, A0A172M477, B3N4V1, B3SVF0, B3SVF1, B4II52, B4PPU5, B4R1P9, B9TQX2, C4YAT5, D0NZB7, D0P1A8, D5L5Q7, E5AD87, G5EHI7, P06498, P0C640, P0C9Y9, P0CAX4, P0CU86, P0DN48, P34553, P34584, P36228, P42634, P55963, P60985, P82701, P83055, P84707, Q09401, Q27002, Q2I2P1, Q32KM8, Q3V2T4, Q3YEH4, Q4TTN8, Q566V9

Diamond homologs: P60985, P85411, Q3V2T4, Q52MQ7

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	16
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

547 predictions. Top by Δscore:

Variant	Effect	Δscore
19:35487755:ATAGA:A	acceptor_gain	1.0000
19:35487756:TAGA:T	acceptor_gain	1.0000
19:35487757:AGA:A	acceptor_gain	1.0000
19:35487758:GA:G	acceptor_gain	1.0000
19:35487759:ACT:A	acceptor_loss	1.0000
19:35487760:C:CC	acceptor_gain	1.0000
19:35487760:CTAAA:C	acceptor_loss	1.0000
19:35488436:CTCA:C	donor_loss	1.0000
19:35488437:TCA:T	donor_loss	1.0000
19:35488438:CA:C	donor_loss	1.0000
19:35488439:A:AG	donor_loss	1.0000
19:35488440:C:CG	donor_loss	1.0000
19:35488483:CGC:C	acceptor_gain	1.0000
19:35488484:GCC:G	acceptor_loss	1.0000
19:35488485:CCT:C	acceptor_loss	1.0000
19:35488486:C:CC	acceptor_gain	1.0000
19:35488660:A:AC	donor_gain	1.0000
19:35488661:C:CC	donor_gain	1.0000
19:35488661:CAGAT:C	donor_gain	1.0000
19:35488797:CTTA:C	donor_loss	1.0000
19:35488799:TA:T	donor_loss	1.0000
19:35488800:A:AC	donor_gain	1.0000
19:35488800:A:AG	donor_loss	1.0000
19:35488801:C:CC	donor_gain	1.0000
19:35488801:CCT:C	donor_gain	1.0000
19:35490352:TCACC:T	donor_loss	1.0000
19:35490353:CACCT:C	donor_loss	1.0000
19:35487707:CTTA:C	donor_loss	0.9900
19:35487709:TA:T	donor_loss	0.9900
19:35487711:C:CT	donor_loss	0.9900

AlphaMissense

638 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:35487727:C:A	W82C	0.996
19:35487727:C:G	W82C	0.996
19:35488456:C:A	W66C	0.990
19:35488456:C:G	W66C	0.990
19:35487729:A:G	W82R	0.989
19:35487729:A:T	W82R	0.989
19:35488458:A:G	W66R	0.988
19:35488458:A:T	W66R	0.988
19:35487751:T:A	K74N	0.985
19:35487751:T:G	K74N	0.985
19:35487755:A:T	I73N	0.980
19:35488465:G:C	F63L	0.977
19:35488465:G:T	F63L	0.977
19:35488467:A:G	F63L	0.977
19:35487736:G:C	F79L	0.976
19:35487736:G:T	F79L	0.976
19:35487738:A:G	F79L	0.976
19:35487737:A:C	F79C	0.974
19:35487737:A:G	F79S	0.972
19:35487752:T:A	K74I	0.969
19:35488466:A:C	F63C	0.969
19:35488459:G:C	N65K	0.967
19:35488459:G:T	N65K	0.967
19:35487734:A:T	L80H	0.965
19:35487743:A:G	L77P	0.960
19:35488460:T:A	N65I	0.958
19:35488448:A:T	L69H	0.955
19:35487460:C:G	G90R	0.952
19:35487460:C:T	G90R	0.952
19:35487728:C:G	W82S	0.951

dbSNP variants (sampled 300 via entrez): RS1000184906 (19:35488540 T>C), RS1000258648 (19:35488376 G>A,C), RS1000519343 (19:35489729 G>A,T), RS1000592746 (19:35489501 C>T), RS1001481896 (19:35490500 A>T), RS1001765940 (19:35490809 C>T), RS1003107249 (19:35487035 C>A,T), RS1003322524 (19:35489442 GTTTGAATTAGACAT>G), RS1003377909 (19:35488141 G>A), RS1003898917 (19:35489513 G>A,T), RS1004495555 (19:35489820 A>G,T), RS1004891357 (19:35488207 A>G), RS1006623483 (19:35487178 T>C), RS1006767 (19:35488960 A>G), RS1006852674 (19:35487204 C>A,T)

Disease associations

OMIM: gene MIM:617212 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

13 total (human), top 13 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, increases methylation	4
aristolochic acid I	increases expression	1
propionaldehyde	increases expression	1
trichostatin A	decreases expression	1
sodium arsenite	decreases expression	1
butyraldehyde	increases expression	1
pentanal	increases expression	1
CGP 52608	affects binding, increases reaction	1
Aldehydes	increases expression	1
Antimony Potassium Tartrate	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Diethylhexyl Phthalate	decreases expression	1
beta-Naphthoflavone	increases expression	1

Clinical trials (associated diseases)

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