CRCT1

Summary

CRCT1 (cysteine rich C-terminal 1, HGNC:29875) is a protein-coding gene on chromosome 1q21.3, encoding Cysteine-rich C-terminal protein 1 (Q9UGL9).

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 24 total
• MANE Select transcript: NM_019060

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29875
Approved symbol	CRCT1
Name	cysteine rich C-terminal 1
Location	1q21.3
Locus type	gene with protein product
Status	Approved
Aliases	NICE-1
Ensembl gene	ENSG00000169509
Ensembl biotype	protein_coding
OMIM	617426
Entrez	54544

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000368790

RefSeq mRNA: 1 — MANE Select: NM_019060 NM_019060

CCDS: CCDS1012

Canonical transcript exons

ENST00000368790 — 2 exons

Exon	Start	End
ENSE00001177309	152514482	152514552
ENSE00001402226	152515362	152516008

Expression profiles

Bgee: expression breadth ubiquitous, 160 present calls, max score 99.93.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 4.3626 / max 1151.2878, expressed in 85 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
5302	4.3333	84
5303	0.0107	5
5305	0.0096	6
5304	0.0089	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	99.93	gold quality
buccal mucosa cell	CL:0002336	99.90	gold quality
amniotic fluid	UBERON:0000173	99.28	gold quality
pharyngeal mucosa	UBERON:0000355	99.23	gold quality
tongue squamous epithelium	UBERON:0006919	98.67	gold quality
esophagus squamous epithelium	UBERON:0006920	98.20	gold quality
esophagus mucosa	UBERON:0002469	97.89	gold quality
cervix squamous epithelium	UBERON:0006922	97.80	silver quality
epithelium of esophagus	UBERON:0001976	97.64	gold quality
oral cavity	UBERON:0000167	97.01	gold quality
skin of leg	UBERON:0001511	96.76	gold quality
squamous epithelium	UBERON:0006914	96.44	gold quality
upper leg skin	UBERON:0004262	95.74	gold quality
skin of abdomen	UBERON:0001416	95.70	gold quality
upper arm skin	UBERON:0004263	95.07	gold quality
cervix epithelium	UBERON:0004801	94.98	gold quality
body of tongue	UBERON:0011876	94.92	gold quality
periodontal ligament	UBERON:0008266	94.84	gold quality
zone of skin	UBERON:0000014	94.80	gold quality
gingiva	UBERON:0001828	92.81	gold quality
gingival epithelium	UBERON:0001949	90.69	gold quality
penis	UBERON:0000989	87.77	gold quality
mammalian vulva	UBERON:0000997	87.46	gold quality
tongue	UBERON:0001723	84.17	gold quality
vagina	UBERON:0000996	83.97	gold quality
nipple	UBERON:0002030	81.68	gold quality
esophagus	UBERON:0001043	81.44	gold quality
uterine cervix	UBERON:0000002	75.50	gold quality
skin of hip	UBERON:0001554	74.75	gold quality
oviduct epithelium	UBERON:0004804	73.24	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-HCAD-1	yes	29286.75
E-ANND-3	yes	3.94

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

31 targeting CRCT1, 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-4500	99.99	72.72	2367
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-130A-3P	99.90	73.31	1861
HSA-MIR-130B-3P	99.90	73.27	1850
HSA-MIR-301A-3P	99.90	73.15	1839
HSA-MIR-301B-3P	99.90	73.19	1836
HSA-MIR-3666	99.90	73.24	1833
HSA-MIR-4295	99.90	73.11	1838
HSA-MIR-489-3P	99.80	66.46	839
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-4270	99.02	66.26	1987
HSA-MIR-4650-3P	99.01	68.39	1062
HSA-MIR-520G-3P	98.91	67.38	1914
HSA-MIR-520H	98.91	67.38	1914
HSA-MIR-6754-5P	98.60	65.54	1627
HSA-MIR-6827-5P	98.46	64.88	1256
HSA-MIR-6831-5P	98.26	67.20	990
HSA-MIR-637	97.91	64.05	1517
HSA-MIR-3927-3P	97.68	66.76	892
HSA-MIR-4790-5P	96.67	67.45	167

Literature-anchored findings (GeneRIF, showing 1)

• CRCT1 functions as a tumor suppressor gene in ESCC and is regulated by miR-520 g, providing potential therapeutic targets for the treatment of ESCC (PMID:26718216)

Cross-species orthologs

0 orthologs

Protein

Protein identifiers

Cysteine-rich C-terminal protein 1 — Q9UGL9 (reviewed: Q9UGL9)

Alternative names: Protein NICE-1

All UniProt accessions (1): Q9UGL9

RefSeq proteins (1): NP_061933* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR031698	NICE-1	Family

Pfam: PF15845

UniProt features (6 total): region of interest 2, compositionally biased region 2, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UGL9-F1	53.29	0.00

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 69 (showing top): FREAC2_01, GCANCTGNY_MYOD_Q6, CAGCTG_AP4_Q5, ONDER_CDH1_TARGETS_3_DN, FREAC3_01, YAMASHITA_METHYLATED_IN_PROSTATE_CANCER, FREAC4_01, E12_Q6, RICKMAN_HEAD_AND_NECK_CANCER_C, TGGAAA_NFAT_Q4_01, chr1q21, COULOUARN_TEMPORAL_TGFB1_SIGNATURE_UP, TCANNTGAY_SREBP1_01, LIN_SILENCED_BY_TUMOR_MICROENVIRONMENT, BRUINS_UVC_RESPONSE_VIA_TP53_GROUP_B

GO Biological Process (0):

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

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	1

Protein interactions and networks

STRING

514 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CRCT1	LTAP1	Q9BWL3	657
CRCT1	S100A7A	Q86SG5	621
CRCT1	CRNN	Q9UBG3	571
CRCT1	KPLCE	Q5T750	555
CRCT1	KPRP	Q5T749	530
CRCT1	SPRR3	Q9UBC9	507
CRCT1	UBAP2L	Q14157	477
CRCT1	CRTC1	Q6UUV9	474
CRCT1	LELP1	Q5T871	474
CRCT1	PRR9	Q5T870	452
CRCT1	SBSN	Q6UWP8	447
CRCT1	LINGO4	Q6UY18	440
CRCT1	FAM25A	B3EWG3	418
CRCT1	CNFN	Q9BYD5	417
CRCT1	KRTDAP	P60985	404

IntAct

215 interactions, top by confidence:

A	B	Type	Score
CRCT1	KRTAP4-12	psi-mi:“MI:0915”(physical association)	0.780
KRTAP4-2	CRCT1	psi-mi:“MI:0915”(physical association)	0.780
KRTAP4-12	CRCT1	psi-mi:“MI:0915”(physical association)	0.780
CRCT1	KRTAP4-2	psi-mi:“MI:0915”(physical association)	0.780
CRCT1	RGS20	psi-mi:“MI:0915”(physical association)	0.720
CRCT1	KRTAP5-9	psi-mi:“MI:0915”(physical association)	0.720
NUP62	CRCT1	psi-mi:“MI:0915”(physical association)	0.720
CRCT1	KRTAP10-7	psi-mi:“MI:0915”(physical association)	0.720
KRTAP10-8	CRCT1	psi-mi:“MI:0915”(physical association)	0.720
CRCT1	KRTAP10-9	psi-mi:“MI:0915”(physical association)	0.720
CRCT1	KRTAP10-8	psi-mi:“MI:0915”(physical association)	0.720
KRTAP10-9	CRCT1	psi-mi:“MI:0915”(physical association)	0.720
RGS20	CRCT1	psi-mi:“MI:0915”(physical association)	0.720
CRCT1	NUP62	psi-mi:“MI:0915”(physical association)	0.720
KRTAP10-7	CRCT1	psi-mi:“MI:0915”(physical association)	0.720

BioGRID (73): CRCT1 (Two-hybrid), CRCT1 (Two-hybrid), CRCT1 (Two-hybrid), CRCT1 (Two-hybrid), AGTRAP (Two-hybrid), KRTAP4-12 (Two-hybrid), KRTAP4-2 (Two-hybrid), KRTAP10-7 (Two-hybrid), KRTAP10-9 (Two-hybrid), KRTAP10-8 (Two-hybrid), NOTCH2NL (Two-hybrid), CRCT1 (Affinity Capture-MS), CRCT1 (Proximity Label-MS), CRCT1 (Two-hybrid), APLP1 (Two-hybrid)

ESM2 similar proteins: A0A286YEV6, A0A286YEX9, A0A286YEY9, A0A286YF01, A0A286YF46, A0A286YF60, A0A286YF77, A0A286YFB4, A0A286YFG1, O14633, P02438, P04459, P05687, P05688, P08131, P08175, P0DSO2, P20730, Q01642, Q01643, Q01644, Q01645, Q07627, Q3LI58, Q3LI59, Q3V2C1, Q5T750, Q5T752, Q5T754, Q5TA78, Q5TA79, Q5TA81, Q5TA82, Q5TCM9, Q8IUC1, Q8IUG1, Q9BQ66, Q9BYP8, Q9BYQ5, Q9BYQ6

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 53 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Keratinization	25	32.4×	5e-31
Formation of the cornified envelope	6	12.3×	5e-04

GO biological processes:

GO term	Partners	Fold	FDR
hair cycle	5	126.5×	1e-07
keratinization	5	31.6×	8e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	21
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

159 predictions. Top by Δscore:

Variant	Effect	Δscore
1:152514548:GTCTG:G	donor_gain	0.9800
1:152514553:G:GC	donor_loss	0.9800
1:152514553:G:GG	donor_gain	0.9800
1:152514554:TAAGT:T	donor_loss	0.9800
1:152515358:CCA:C	acceptor_loss	0.9800
1:152515359:CA:C	acceptor_loss	0.9800
1:152515360:A:AT	acceptor_loss	0.9800
1:152515361:GGTTT:G	acceptor_gain	0.9700
1:152515360:A:AG	acceptor_gain	0.9400
1:152515361:G:GG	acceptor_gain	0.9400
1:152514556:AGTCT:A	donor_loss	0.8500
1:152515361:GGT:G	acceptor_gain	0.8500
1:152514550:CTG:C	donor_gain	0.8400
1:152515360:AG:A	acceptor_gain	0.8400
1:152515361:GG:G	acceptor_gain	0.8400
1:152514525:G:GG	donor_gain	0.8200
1:152514549:TCTG:T	donor_gain	0.8200
1:152515256:AGGC:A	acceptor_gain	0.8200
1:152514524:A:AG	donor_gain	0.8100
1:152515361:GGTT:G	acceptor_gain	0.8000
1:152514551:TG:T	donor_gain	0.7900
1:152514552:GG:G	donor_gain	0.7900
1:152514522:GTA:G	donor_gain	0.7800
1:152514553:GTAA:G	donor_gain	0.7000
1:152514551:TGG:T	donor_gain	0.6800
1:152515233:G:A	acceptor_gain	0.6800
1:152514554:TAAG:T	donor_gain	0.6700
1:152514555:AAGT:A	donor_gain	0.6700
1:152514550:CTGG:C	donor_gain	0.6500
1:152514552:GGTAA:G	donor_gain	0.6400

AlphaMissense

630 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:152515420:T:C	F13L	0.934
1:152515422:T:A	F13L	0.934
1:152515422:T:G	F13L	0.934
1:152515428:G:C	K15N	0.866
1:152515428:G:T	K15N	0.866
1:152515567:T:C	C62R	0.849
1:152515415:A:T	K11I	0.834
1:152515569:C:G	C62W	0.831
1:152515429:G:A	G16R	0.818
1:152515429:G:C	G16R	0.818
1:152515429:G:T	G16W	0.809
1:152515581:A:C	R66S	0.807
1:152515581:A:T	R66S	0.807
1:152515582:C:A	R67S	0.806
1:152515666:T:C	C95R	0.790
1:152515537:T:C	C52R	0.770
1:152515570:T:C	F63L	0.769
1:152515572:C:A	F63L	0.769
1:152515572:C:G	F63L	0.769
1:152515427:A:T	K15M	0.766
1:152515416:A:C	K11N	0.758
1:152515416:A:T	K11N	0.758
1:152515561:T:C	C60R	0.757
1:152515498:T:C	C39R	0.751
1:152515580:G:C	R66T	0.744
1:152515627:A:C	S82R	0.742
1:152515629:C:A	S82R	0.742
1:152515629:C:G	S82R	0.742
1:152515540:T:C	C53R	0.740
1:152515668:C:G	C95W	0.736

dbSNP variants (sampled 300 via entrez): RS1000945768 (1:152515182 A>G), RS1001119443 (1:152514578 G>A,C), RS1001708475 (1:152515955 A>G), RS1002123755 (1:152515752 G>A,T), RS1002177519 (1:152515999 C>G), RS1003614322 (1:152514669 C>A,G,T), RS1004069400 (1:152516451 G>A,C), RS1004422490 (1:152516180 C>A,G,T), RS1004585148 (1:152512807 G>A,T), RS1005020913 (1:152513096 G>T), RS1005472795 (1:152513067 T>A), RS1005523855 (1:152513573 T>C), RS1005901187 (1:152516334 G>C), RS1007417321 (1:152513952 C>T), RS1007770018 (1:152513711 G>A,C)

Disease associations

OMIM: gene MIM:617426 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST001182_5	Asthma	6.000000e-06
GCST001762_428	Obesity-related traits	3.000000e-06
GCST003184_30	Atopic dermatitis	6.000000e-29
GCST005005_6	Plantar warts	5.000000e-09
GCST007563_33	Allergic disease (asthma, hay fever or eczema)	3.000000e-11
GCST007564_24	Asthma or allergic disease (pleiotropy)	5.000000e-12
GCST008916_75	Asthma	2.000000e-08
GCST008916_82	Asthma	5.000000e-27
GCST008916_88	Asthma	1.000000e-25

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0008406	susceptibility to plantar warts measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

16 total (human), top 16 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Tetrachlorodibenzodioxin	increases expression	2
Particulate Matter	increases expression	2
arsenite	increases methylation	1
sodium arsenite	increases expression	1
hydroquinone	increases expression	1
obeticholic acid	decreases expression	1
Arsenicals	increases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Folic Acid	decreases expression	1
Nicotine	increases expression	1
Silicon Dioxide	increases expression	1
Sodium Dodecyl Sulfate	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Cyclosporine	decreases expression	1
Asbestos, Crocidolite	increases expression	1
Lactic Acid	decreases expression	1

Clinical trials (associated diseases)

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