RPTN

Summary

RPTN (repetin, HGNC:26809) is a protein-coding gene on chromosome 1q21.3, encoding Repetin (Q6XPR3). Involved in the cornified cell envelope formation.

Predicted to enable calcium ion binding activity and transition metal ion binding activity. Predicted to be located in cytosol. Predicted to be active in cornified envelope.

Source: NCBI Gene 126638 — RefSeq curated summary.

At a glance

• GWAS associations: 18
• Clinical variants (ClinVar): 111 total
• MANE Select transcript: NM_001122965

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26809
Approved symbol	RPTN
Name	repetin
Location	1q21.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ39117
Ensembl gene	ENSG00000215853
Ensembl biotype	protein_coding
OMIM	613259
Entrez	126638

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000316073

RefSeq mRNA: 1 — MANE Select: NM_001122965 NM_001122965

CCDS: CCDS41397

Canonical transcript exons

ENST00000316073 — 3 exons

Exon	Start	End
ENSE00001235715	152153595	152156960
ENSE00001447991	152157752	152157909
ENSE00001447992	152159184	152159228

Expression profiles

Bgee: expression breadth broad, 57 present calls, max score 87.89.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1745 / max 107.2182, expressed in 31 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
14536	0.1745	31

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
gingiva	UBERON:0001828	87.89	gold quality
gingival epithelium	UBERON:0001949	84.31	gold quality
tongue	UBERON:0001723	78.36	gold quality
body of tongue	UBERON:0011876	74.97	gold quality
superior surface of tongue	UBERON:0007371	74.75	gold quality
skin of leg	UBERON:0001511	73.59	gold quality
sperm	CL:0000019	72.53	silver quality
amniotic fluid	UBERON:0000173	72.39	gold quality
epithelium of nasopharynx	UBERON:0001951	72.33	gold quality
zone of skin	UBERON:0000014	71.37	gold quality
skin of hip	UBERON:0001554	71.10	gold quality
nasal cavity epithelium	UBERON:0005384	68.68	silver quality
skin of abdomen	UBERON:0001416	68.21	gold quality
oral cavity	UBERON:0000167	66.72	gold quality
tonsil	UBERON:0002372	65.68	gold quality
upper leg skin	UBERON:0004262	64.62	gold quality
mammalian vulva	UBERON:0000997	61.14	silver quality
penis	UBERON:0000989	60.31	gold quality
lower esophagus mucosa	UBERON:0035834	53.54	gold quality
vagina	UBERON:0000996	52.27	gold quality
esophagus squamous epithelium	UBERON:0006920	50.81	silver quality
ectocervix	UBERON:0012249	50.68	gold quality
esophagus mucosa	UBERON:0002469	48.67	gold quality
pharyngeal mucosa	UBERON:0000355	45.83	gold quality
uterine cervix	UBERON:0000002	45.26	gold quality
islet of Langerhans	UBERON:0000006	44.57	gold quality
lower lobe of lung	UBERON:0008949	43.44	silver quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	43.37	gold quality
nasal cavity mucosa	UBERON:0001826	42.72	silver quality
secondary oocyte	CL:0000655	42.57	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.27

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

69 targeting RPTN, 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-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-8075	99.97	67.20	962
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-130B-5P	99.83	68.50	1888
HSA-MIR-4420	99.82	70.08	1624
HSA-MIR-181B-2-3P	99.81	70.06	1646
HSA-MIR-181B-3P	99.81	70.06	1646
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-5580-3P	99.70	69.41	2052
HSA-MIR-5093	99.67	69.26	2291
HSA-MIR-7156-5P	99.64	68.81	1369
HSA-MIR-4756-3P	99.62	66.30	1319
HSA-MIR-7844-5P	99.55	68.56	1428
HSA-MIR-4273	99.45	67.93	1206
HSA-MIR-6165	99.44	67.12	1389
HSA-MIR-3911	99.38	66.95	1087
HSA-MIR-12113	99.32	67.54	1072
HSA-MIR-2115-3P	99.31	69.68	2026
HSA-MIR-580-5P	99.28	70.94	1776
HSA-MIR-3191-5P	99.24	66.52	1722
HSA-MIR-4279	99.19	66.70	2437
HSA-MIR-1253	99.12	67.08	1688
HSA-MIR-877-3P	99.09	68.10	1637
HSA-MIR-4711-3P	98.97	66.87	1020
HSA-MIR-6760-5P	98.87	66.73	1515

Literature-anchored findings (GeneRIF, showing 3)

• RPTN plays a potential role in emotional and cognitive processing; its decrease in serum may indicate its involvement in the pathogenesis of schizophrenia and bipolar disorder (PMID:25613293)
• The single-nucleotide polymorphisms of CRNN (rs941934) and RPTN (rs3001978, rs28441202) may contribute to Atopic Dermatitis development, but further studies on a larger group of Atopic Dermatitis patients are needed to verify this assumption. (PMID:28219068)
• Letter: RPTN gene is associated with straight hair in Europeans and East Asians. Genetics of straight hair may to some degree overlap between these two ancestry groups. (PMID:29935789)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Rptn	ENSMUSG00000041984
rattus_norvegicus	Rptn	ENSRNOG00000018679

Paralogs (3): FLG2 (ENSG00000143520), FLG (ENSG00000143631), HRNR (ENSG00000197915)

Protein

Protein identifiers

Repetin — Q6XPR3 (reviewed: Q6XPR3)

All UniProt accessions (1): Q6XPR3

UniProt curated annotations — full annotation on UniProt →

Function. Involved in the cornified cell envelope formation. Multifunctional epidermal matrix protein. Reversibly binds calcium.

Subcellular location. Secreted. Extracellular space. Extracellular matrix.

Tissue specificity. Expression is scattered in the normal epidermis but strong in the acrosyringium, the inner hair root sheath and in the filiform papilli of the tongue.

Post-translational modifications. Potential substrate of transglutaminase. Some arginines are probably converted to citrullines by peptidylarginine deimidase.

Domain organisation. Can be divided into a N-terminal domain with significant homology to S100-like calcium-binding proteins, a central domain containing a series of short tandem repeats, and two flanking segments with low homology to the consensus sequences of the central repeats.

Similarity. Belongs to the S100-fused protein family.

RefSeq proteins (1): NP_001116437* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001751	S100/CaBP7/8-like_CS	Conserved_site
IPR002048	EF_hand_dom	Domain
IPR011992	EF-hand-dom_pair	Homologous_superfamily
IPR013787	S100_Ca-bd_sub	Domain
IPR018247	EF_Hand_1_Ca_BS	Binding_site
IPR034325	S-100_dom	Domain

Pfam: PF01023

UniProt features (25 total): compositionally biased region 10, binding site 6, region of interest 5, domain 2, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6XPR3-F1	42.63	0.02

Functional residue map

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

Ligand- & substrate-binding residues (6): 32; 62; 64; 66; 68; 73

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-6809371	Formation of the cornified envelope
R-HSA-1266738	Developmental Biology
R-HSA-6805567	Keratinization

MSigDB gene sets: 72 (showing top): DARWICHE_SKIN_TUMOR_PROMOTER_DN, DARWICHE_PAPILLOMA_RISK_LOW_UP, DARWICHE_PAPILLOMA_RISK_HIGH_UP, DARWICHE_SQUAMOUS_CELL_CARCINOMA_UP, MARTINEZ_RB1_TARGETS_UP, MARTINEZ_RB1_AND_TP53_TARGETS_UP, chr1q21, GOCC_CORNIFIED_ENVELOPE, DODD_NASOPHARYNGEAL_CARCINOMA_DN, RICKMAN_HEAD_AND_NECK_CANCER_E, MARTENS_TRETINOIN_RESPONSE_UP, BRUINS_UVC_RESPONSE_VIA_TP53_GROUP_A, ZWANG_TRANSIENTLY_UP_BY_2ND_EGF_PULSE_ONLY, REACTOME_KERATINIZATION, REACTOME_FORMATION_OF_THE_CORNIFIED_ENVELOPE

GO Biological Process (0):

GO Molecular Function (3): calcium ion binding (GO:0005509), transition metal ion binding (GO:0046914), metal ion binding (GO:0046872)

GO Cellular Component (3): cornified envelope (GO:0001533), cytosol (GO:0005829), extracellular region (GO:0005576)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Keratinization	1
Developmental Biology	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
metal ion binding	2
cellular anatomical structure	2
cation binding	1
plasma membrane	1
cytoplasm	1

Protein interactions and networks

STRING

1403 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RPTN	DEPP1	Q9NTK1	936
RPTN	LCE3C	Q5T5A8	658
RPTN	LORICRIN	P23490	608
RPTN	TCHH	Q07283	604
RPTN	LCE3B	Q5TA77	590
RPTN	S100Z	Q8WXG8	571
RPTN	LCE5A	Q5TCM9	518
RPTN	FLG	P20930	515
RPTN	LCE3A	Q5TA76	511
RPTN	IVL	P07476	510
RPTN	SPRR2A	P35326	483
RPTN	SPRR4	Q96PI1	474
RPTN	LCE1C	Q5T751	442
RPTN	CRNN	Q9UBG3	437
RPTN	OR51Q1	Q8NH59	434
RPTN	LCE3E	Q5T5B0	434

IntAct

6 interactions, top by confidence:

A	B	Type	Score
P		psi-mi:“MI:0914”(association)	0.350
MAP1LC3B		psi-mi:“MI:0914”(association)	0.350
GABARAPL2		psi-mi:“MI:0914”(association)	0.350
GABARAPL1		psi-mi:“MI:0914”(association)	0.350
FNDC5	A2ML1	psi-mi:“MI:0914”(association)	0.350

BioGRID (4): RPTN (Affinity Capture-MS), RPTN (Affinity Capture-MS), RPTN (Affinity Capture-MS), RPTN (Affinity Capture-MS)

ESM2 similar proteins: A0A087WUL8, A0A0J9YWL9, A0A0J9YY54, A0A0U1RQI7, A6NJ88, A6QL64, B4DH59, D3ZVV1, E9Q6E9, F1LWT0, O04492, O88799, P0DKJ7, P0DKJ8, P0DKL2, P0DPF3, P18583, P53353, Q08AG5, Q0P6D6, Q2EG98, Q3BBV2, Q4ZJZ1, Q5HY64, Q5JPF3, Q5QGU6, Q5TAG4, Q5TI25, Q5XHX6, Q6P3W6, Q6P902, Q6XPR3, Q6ZQX7, Q86T75, Q86VE3, Q86VQ3, Q8N2N9, Q8N660, Q8N693, Q96EQ9

Diamond homologs: A6QP92, P20930, P37709, P97347, Q07283, Q2VIS4, Q5D862, Q5QJ38, Q6XPR3, Q9D3P1, Q9UBG3, A7K6Y8, A7K6Y9, O77691, O77791, P02632, P02633, P02634, P02638, P02639, P04271, P04631, P05109, P05942, P05943, P05964, P06702, P06703, P07091, P14069, P22793, P23297, P24479, P24480, P25815, P27004, P27005, P28318, P28782, P28783

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	94
Likely benign	16
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

150 predictions. Top by Δscore:

Variant	Effect	Δscore
1:152156956:GGTCT:G	acceptor_gain	1.0000
1:152156957:GTCT:G	acceptor_gain	1.0000
1:152156958:TCT:T	acceptor_gain	1.0000
1:152156959:CT:C	acceptor_gain	1.0000
1:152156959:CTC:C	acceptor_gain	1.0000
1:152156960:TCT:T	acceptor_gain	1.0000
1:152156961:C:A	acceptor_loss	1.0000
1:152156961:C:CC	acceptor_gain	1.0000
1:152157746:TCTTA:T	donor_loss	1.0000
1:152157747:CTTA:C	donor_loss	1.0000
1:152157748:TTAC:T	donor_loss	1.0000
1:152157749:TA:T	donor_loss	1.0000
1:152157751:C:CT	donor_loss	1.0000
1:152157905:TGAAC:T	acceptor_gain	1.0000
1:152157907:AAC:A	acceptor_gain	1.0000
1:152157908:AC:A	acceptor_gain	1.0000
1:152157909:CC:C	acceptor_gain	1.0000
1:152157910:C:CC	acceptor_gain	1.0000
1:152157910:CT:C	acceptor_loss	1.0000
1:152156961:C:G	acceptor_gain	0.9900
1:152156964:T:C	acceptor_gain	0.9900
1:152156964:T:TC	acceptor_gain	0.9900
1:152157750:A:AC	donor_gain	0.9900
1:152157751:C:CC	donor_gain	0.9900
1:152157906:GAAC:G	acceptor_gain	0.9900
1:152159178:TCTTA:T	donor_loss	0.9900
1:152159179:CTTA:C	donor_loss	0.9900
1:152159180:TTACC:T	donor_loss	0.9900
1:152159181:TAC:T	donor_loss	0.9900
1:152159183:C:CG	donor_loss	0.9900

AlphaMissense

5315 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:152157845:G:C	F15L	0.985
1:152157845:G:T	F15L	0.985
1:152157847:A:G	F15L	0.985
1:152156886:A:C	F71L	0.975
1:152156886:A:T	F71L	0.975
1:152156888:A:G	F71L	0.975
1:152156862:G:C	F79L	0.967
1:152156862:G:T	F79L	0.967
1:152156864:A:G	F79L	0.967
1:152157783:A:G	L36P	0.965
1:152156879:A:C	Y74D	0.964
1:152156879:A:G	Y74H	0.964
1:152156878:T:G	Y74S	0.963
1:152157792:A:G	L33S	0.955
1:152156887:A:G	F71S	0.952
1:152156875:A:G	L75P	0.951
1:152156849:C:G	A84P	0.949
1:152157780:A:G	L37P	0.949
1:152157846:A:G	F15S	0.944
1:152156857:A:G	L81S	0.940
1:152156917:A:G	L61S	0.934
1:152157767:A:C	F41L	0.933
1:152157767:A:T	F41L	0.933
1:152157769:A:G	F41L	0.933
1:152157867:A:T	I8K	0.933
1:152157788:T:A	K34N	0.930
1:152157788:T:G	K34N	0.930
1:152156879:A:T	Y74N	0.929
1:152157780:A:T	L37H	0.929
1:152157756:A:G	L45P	0.925

dbSNP variants (sampled 300 via entrez): RS1000437682 (1:152159010 A>T), RS1000477799 (1:152155338 C>G), RS1001343280 (1:152156412 A>G), RS1002242149 (1:152157014 G>A,T), RS1003780838 (1:152158141 A>G), RS1003957986 (1:152159487 T>C), RS1004687003 (1:152154662 C>T), RS1004984886 (1:152159308 G>A), RS1005967736 (1:152160209 T>C), RS1006198385 (1:152158242 C>G,T), RS1006539203 (1:152154270 C>T), RS1006865090 (1:152154985 G>T), RS1007309974 (1:152155001 C>T), RS1007645567 (1:152160965 A>G), RS1008045936 (1:152160487 G>A)

Disease associations

OMIM: gene MIM:613259 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

18 associations (top):

Study	Trait	p-value
GCST004861_28	Itch intensity from mosquito bite	3.000000e-08
GCST005038_8	Allergic disease (asthma, hay fever or eczema)	7.000000e-17
GCST006661_183	Male-pattern baldness	1.000000e-10
GCST007563_33	Allergic disease (asthma, hay fever or eczema)	3.000000e-11
GCST007564_24	Asthma or allergic disease (pleiotropy)	5.000000e-12
GCST007797_16	Asthma onset (childhood vs adult)	8.000000e-24
GCST007798_7	Asthma	4.000000e-24
GCST007800_52	Asthma (childhood onset)	8.000000e-48
GCST008916_82	Asthma	5.000000e-27
GCST008916_88	Asthma	1.000000e-25
GCST009798_26	Asthma	2.000000e-21
GCST009798_76	Asthma	1.000000e-22
GCST010984_48	Allergic disease (asthma, hay fever and/or eczema) (multivariate analysis)	6.000000e-19
GCST010985_2	Allergic disease (asthma, hay fever and/or eczema) (age of onset)	3.000000e-48
GCST011053_6	Neuroblastoma (pediatric)	8.000000e-23
GCST011379_1	Cutaneous mastocytosis (childhood)	4.000000e-09
GCST011381_4	Cutaneous mastocytosis	3.000000e-11
GCST011383_4	Mastocytosis	8.000000e-12

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0008377	mosquito bite reaction itch intensity measurement
EFO:0004847	age at onset

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

18 total (human), top 18 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Nickel	decreases expression, affects expression, decreases reaction	3
hydroquinone	increases expression	2
Sodium Dodecyl Sulfate	decreases expression, increases expression	2
Tetrachlorodibenzodioxin	increases expression	2
urushiol	increases expression	1
sodium arsenate	decreases expression, increases abundance	1
trichostatin A	affects expression, decreases reaction	1
sodium arsenite	decreases expression	1
avobenzone	decreases expression	1
CGP 52608	affects binding, increases reaction	1
Antimony Potassium Tartrate	decreases expression	1
Arsenic	decreases expression, increases abundance	1
Benzo(a)pyrene	increases methylation	1
Coal Tar	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	decreases expression	1
Aflatoxin B1	decreases methylation	1
Lactic Acid	decreases expression	1

Clinical trials (associated diseases)

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