CNIH1

Summary

CNIH1 (cornichon family member 1, HGNC:19431) is a protein-coding gene on chromosome 14q22.2, encoding Protein cornichon homolog 1 (O95406). Involved in the selective transport and maturation of TGF-alpha family proteins.

Predicted to enable signaling receptor binding activity. Predicted to be involved in immune response and signal transduction. Predicted to be located in ER to Golgi transport vesicle membrane; endoplasmic reticulum membrane; and endoplasmic reticulum-Golgi intermediate compartment membrane.

Source: NCBI Gene 10175 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 12 total
• MANE Select transcript: NM_005776

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19431
Approved symbol	CNIH1
Name	cornichon family member 1
Location	14q22.2
Locus type	gene with protein product
Status	Approved
Aliases	TGAM77, CNIL
Ensembl gene	ENSG00000100528
Ensembl biotype	protein_coding
OMIM	611287
Entrez	10175

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 6 protein_coding, 2 nonsense_mediated_decay

ENST00000216416, ENST00000395573, ENST00000553660, ENST00000554683, ENST00000556113, ENST00000557659, ENST00000557690, ENST00000870898

RefSeq mRNA: 1 — MANE Select: NM_005776 NM_005776

CCDS: CCDS9717

Canonical transcript exons

ENST00000216416 — 5 exons

Exon	Start	End
ENSE00000854780	54441247	54441374
ENSE00003490657	54432108	54432220
ENSE00003631422	54430261	54430404
ENSE00003683874	54436369	54436437
ENSE00003729427	54423561	54427841

Expression profiles

Bgee: expression breadth ubiquitous, 301 present calls, max score 98.52.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 96.5962 / max 487.5155, expressed in 1819 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
143316	96.5962	1819

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
jejunal mucosa	UBERON:0000399	98.52	gold quality
cartilage tissue	UBERON:0002418	98.42	gold quality
pigmented layer of retina	UBERON:0001782	98.23	gold quality
germinal epithelium of ovary	UBERON:0001304	98.08	gold quality
rectum	UBERON:0001052	98.04	gold quality
gall bladder	UBERON:0002110	98.04	gold quality
secondary oocyte	CL:0000655	97.99	gold quality
islet of Langerhans	UBERON:0000006	97.57	gold quality
stromal cell of endometrium	CL:0002255	97.56	gold quality
oocyte	CL:0000023	97.48	gold quality
monocyte	CL:0000576	97.45	gold quality
oral cavity	UBERON:0000167	97.40	gold quality
adrenal tissue	UBERON:0018303	97.34	gold quality
mononuclear cell	CL:0000842	97.33	gold quality
leukocyte	CL:0000738	97.21	gold quality
liver	UBERON:0002107	97.18	gold quality
right lobe of liver	UBERON:0001114	97.12	gold quality
choroid plexus epithelium	UBERON:0003911	97.10	gold quality
parietal pleura	UBERON:0002400	97.06	gold quality
calcaneal tendon	UBERON:0003701	96.87	gold quality
smooth muscle tissue	UBERON:0001135	96.81	gold quality
adult organism	UBERON:0007023	96.68	gold quality
endothelial cell	CL:0000115	96.62	gold quality
pleura	UBERON:0000977	96.58	gold quality
vermiform appendix	UBERON:0001154	96.58	gold quality
right adrenal gland cortex	UBERON:0035827	96.46	gold quality
right adrenal gland	UBERON:0001233	96.43	gold quality
mucosa of transverse colon	UBERON:0004991	96.37	gold quality
left adrenal gland	UBERON:0001234	96.29	gold quality
ventricular zone	UBERON:0003053	96.20	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-CURD-89	yes	486.23
E-HCAD-13	yes	12.50
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CTCF

miRNA regulators (miRDB)

134 targeting CNIH1, 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-6873-3P	100.00	71.42	2626
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515

Literature-anchored findings (GeneRIF, showing 3)

• human CNIH and Drosophila Cni are primarily localized in the endoplasmic reticulum and associate with immature TGFalpha family proteins; alterations of cornichon expression result in changes in transport, processing and secretion of TGFalpha proteins (PMID:17607000)
• the modulation of AMPA receptors by CNIH-2 depends upon the Transmembrane AMPA receptor regulatory protein isoform composition within the receptor complex (PMID:22211840)
• Significant upregulation of CNIH-1 mRNA expression was found in schizophrenia. (PMID:23103966)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Cnih1	ENSMUSG00000015759
rattus_norvegicus	Cnih1	ENSRNOG00000009811
drosophila_melanogaster	cni	FBGN0000339
caenorhabditis_elegans		WBGENE00011648

Paralogs (4): PPCS (ENSG00000127125), CNIH4 (ENSG00000143771), CNIH3 (ENSG00000143786), CNIH2 (ENSG00000174871)

Protein

Protein identifiers

Protein cornichon homolog 1 — O95406 (reviewed: O95406)

Alternative names: Cornichon family AMPA receptor auxiliary protein 1, Protein cornichon homolog, T-cell growth-associated molecule 77

All UniProt accessions (8): O95406, A8MVW4, B2R4P1, G3V3B2, G3V474, G3V4K0, G3V5P8, G3V5Q6

UniProt curated annotations — full annotation on UniProt →

Function. Involved in the selective transport and maturation of TGF-alpha family proteins.

Subunit / interactions. Interacts with AREG immature precursor and with immature TGFA, i.e. with a prosegment and lacking full N-glycosylation, but not with the fully N-glycosylated form. In the Golgi apparatus, may form a complex with GORASP55 and transmembrane TGFA.

Subcellular location. Endoplasmic reticulum membrane. Golgi apparatus membrane.

Tissue specificity. Highly expressed in heart, liver, skeletal muscle, pancreas, adrenal medulla and cortex, thyroid, testis, spleen, appendix, peripheral blood lymphocytes and bone marrow. Lower expression found in brain, placenta, lung, kidney, ovary, small intestine, stomach, lymph node, thymus and fetal liver. Expression is up-regulated in dorsolateral prefrontal cortex of patients with schizophrenia (postmortem brain study).

Similarity. Belongs to the cornichon family.

RefSeq proteins (1): NP_005767* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003377	Cornichon	Family
IPR033466	Cornichon_conserved	Conserved_site

Pfam: PF03311

UniProt features (8 total): topological domain 4, transmembrane region 3, chain 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
9OVV	ELECTRON MICROSCOPY	3.76

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95406-F1	84.77	0.29

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-204005	COPII-mediated vesicle transport
R-HSA-5694530	Cargo concentration in the ER

MSigDB gene sets: 233 (showing top): ACTACCT_MIR196A_MIR196B, MORF_MBD4, MORF_RAB5A, KAAB_FAILED_HEART_ATRIUM_DN, GGGNRMNNYCAT_UNKNOWN, MODULE_151, MORF_RAD21, GOBP_VESICLE_MEDIATED_TRANSPORT, REACTOME_MEMBRANE_TRAFFICKING, MORF_PSMC2, COUP_01, PUJANA_CHEK2_PCC_NETWORK, MORF_SKP1A, MODULE_239, MORF_ATOX1

GO Biological Process (3): immune response (GO:0006955), signal transduction (GO:0007165), vesicle-mediated transport (GO:0016192)

GO Molecular Function (2): signaling receptor binding (GO:0005102), protein binding (GO:0005515)

GO Cellular Component (7): Golgi membrane (GO:0000139), endoplasmic reticulum membrane (GO:0005789), ER to Golgi transport vesicle membrane (GO:0012507), endoplasmic reticulum-Golgi intermediate compartment membrane (GO:0033116), endoplasmic reticulum (GO:0005783), Golgi apparatus (GO:0005794), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
ER to Golgi Anterograde Transport	2

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular process	2
bounding membrane of organelle	2
cytoplasm	2
endomembrane system	2
intracellular membrane-bounded organelle	2
immune system process	1
response to stimulus	1
cell communication	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
transport	1
protein binding	1
binding	1
Golgi apparatus	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
COPII-coated ER to Golgi transport vesicle	1
transport vesicle membrane	1
coated vesicle membrane	1
endoplasmic reticulum-Golgi intermediate compartment	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1140 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CNIH1	GRIA1	P42261	899
CNIH1	NT5C1A	Q9BXI3	865
CNIH1	CACNG8	Q8WXS5	752
CNIH1	SHISA9	B4DS77	734
CNIH1	GSG1L	Q6UXU4	725
CNIH1	GRIA4	P48058	696
CNIH1	GRIA2	P42262	672
CNIH1	GRIA3	P42263	650
CNIH1	TGFA	P01135	632
CNIH1	GSG1L2	A8MUP6	624
CNIH1	SYNDIG1	Q9H7V2	614
CNIH1	COL21A1	Q96P44	599
CNIH1	CACNG2	Q9Y698	597
CNIH1	ADAMTS14	Q8WXS8	586
CNIH1	COL4A6	Q14031	557

IntAct

93 interactions, top by confidence:

A	B	Type	Score
CNIH1	SMIM3	psi-mi:“MI:0915”(physical association)	0.600
CNIH1	MCEMP1	psi-mi:“MI:0915”(physical association)	0.560
CNIH1	MFF	psi-mi:“MI:0915”(physical association)	0.560
CNIH1	OPRM1	psi-mi:“MI:0915”(physical association)	0.560
CNIH1	LRRC59	psi-mi:“MI:0915”(physical association)	0.560
CNIH1	BIK	psi-mi:“MI:0915”(physical association)	0.560
CNIH1	GPX8	psi-mi:“MI:0915”(physical association)	0.560
CNIH1	CLDN7	psi-mi:“MI:0915”(physical association)	0.560
LEUTX	CNIH1	psi-mi:“MI:0915”(physical association)	0.560
CNIH1	SLC10A6	psi-mi:“MI:0915”(physical association)	0.560
CNIH1	AQP6	psi-mi:“MI:0915”(physical association)	0.560
CNIH1	TMEM52B	psi-mi:“MI:0915”(physical association)	0.560
CNIH1	SLC18A1	psi-mi:“MI:0915”(physical association)	0.560
CNIH1	ERGIC3	psi-mi:“MI:0915”(physical association)	0.560
CNIH1	CD79A	psi-mi:“MI:0915”(physical association)	0.560
CNIH1	CYB5R3	psi-mi:“MI:0915”(physical association)	0.560
CNIH1	MRM1	psi-mi:“MI:0915”(physical association)	0.560
FFAR2	CNIH1	psi-mi:“MI:0915”(physical association)	0.560
CNIH1	RNF24	psi-mi:“MI:0915”(physical association)	0.560
	CNIH1	psi-mi:“MI:0915”(physical association)	0.560
CNIH1	GPR152	psi-mi:“MI:0915”(physical association)	0.560
CNIH1	SLC35C2	psi-mi:“MI:0915”(physical association)	0.560
CNIH1	HTR2C	psi-mi:“MI:0915”(physical association)	0.560
CNIH1	EVI2B	psi-mi:“MI:0915”(physical association)	0.560
SLC22A23	CNIH1	psi-mi:“MI:0915”(physical association)	0.560
CNIH1	FAM209A	psi-mi:“MI:0915”(physical association)	0.560
CNIH1	SHISA4	psi-mi:“MI:0915”(physical association)	0.560
CNIH1	CD53	psi-mi:“MI:0915”(physical association)	0.560
CNIH1	CPLX4	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (36): CNIH1 (Synthetic Lethality), CNIH1 (Two-hybrid), CNIH1 (Two-hybrid), CNIH1 (Two-hybrid), CNIH1 (Two-hybrid), CNIH1 (Two-hybrid), RNF24 (Two-hybrid), CD79A (Two-hybrid), LRRC59 (Two-hybrid), OPRM1 (Two-hybrid), FAM209A (Two-hybrid), ERGIC3 (Two-hybrid), FFAR2 (Two-hybrid), SLC22A23 (Two-hybrid), CD53 (Two-hybrid)

ESM2 similar proteins: A0JN27, A6NI61, A6QQ59, B0CM95, B0KWE9, B1MTH4, B2KI79, B2RZC9, D0Q0Y7, O35089, O35372, O95406, P22234, P51583, P86229, Q0X0A5, Q13888, Q2TBV5, Q2YDL1, Q3KNM2, Q3ZC24, Q3ZCD7, Q5BIN6, Q5BJU5, Q5R589, Q5RB59, Q5RDB5, Q5RL79, Q64232, Q6P1K8, Q6PI25, Q6ZWS4, Q86YN1, Q8CFD0, Q8IZV2, Q8N6L1, Q8NFT2, Q8NFX7, Q8R3T5, Q8TBE1

Diamond homologs: D0Q0Y7, O35089, O35372, O95406, P49858, P52159, Q0VFK3, Q22361, Q3T126, Q401C0, Q5BIN6, Q5BJU5, Q5BL21, Q5R9M4, Q5RDB5, Q68EY2, Q6P3N5, Q6PI25, Q6ZWS4, Q8TBE1, Q9CX13, Q9P003, O14038, P38312, P53173, Q0DET3, Q2QQ55, Q8GWT5, Q9C7D7, Q9P6K6, Q9SZ74, Q3EDD7, Q84W04

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	11
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1034 predictions. Top by Δscore:

Variant	Effect	Δscore
14:54427704:A:C	donor_gain	1.0000
14:54427728:CTTGG:C	donor_gain	1.0000
14:54427787:A:C	donor_gain	1.0000
14:54427837:TCATG:T	acceptor_gain	1.0000
14:54427838:CATG:C	acceptor_gain	1.0000
14:54427838:CATGC:C	acceptor_gain	1.0000
14:54427840:TG:T	acceptor_gain	1.0000
14:54427842:C:CC	acceptor_gain	1.0000
14:54430315:T:TA	donor_gain	1.0000
14:54436367:A:AC	donor_gain	1.0000
14:54436368:C:CC	donor_gain	1.0000
14:54436434:TAAT:T	acceptor_gain	1.0000
14:54436437:TCTAA:T	acceptor_loss	1.0000
14:54436438:C:A	acceptor_loss	1.0000
14:54436438:C:CC	acceptor_gain	1.0000
14:54441241:ACT:A	donor_loss	1.0000
14:54441242:CTC:C	donor_loss	1.0000
14:54441243:TCA:T	donor_loss	1.0000
14:54441244:CA:C	donor_loss	1.0000
14:54441245:A:AC	donor_gain	1.0000
14:54441246:C:CA	donor_gain	1.0000
14:54441246:CG:C	donor_gain	1.0000
14:54441246:CGT:C	donor_gain	1.0000
14:54441246:CGTG:C	donor_gain	1.0000
14:54427709:T:C	donor_gain	0.9900
14:54427839:ATGCT:A	acceptor_loss	0.9900
14:54427841:GCTGA:G	acceptor_loss	0.9900
14:54427842:C:CA	acceptor_loss	0.9900
14:54427843:T:A	acceptor_loss	0.9900
14:54430311:T:TA	donor_gain	0.9900

AlphaMissense

954 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:54436418:A:G	L34P	1.000
14:54430302:T:A	K122N	0.999
14:54430302:T:G	K122N	0.999
14:54430351:A:T	I106N	0.999
14:54436384:A:C	C45W	0.999
14:54436385:C:T	C45Y	0.999
14:54436397:G:T	P41H	0.999
14:54436418:A:T	L34Q	0.999
14:54436431:C:G	A30P	0.999
14:54436433:A:T	I29K	0.999
14:54441275:G:T	A18D	0.999
14:54430267:A:G	L134P	0.998
14:54430278:A:C	F130L	0.998
14:54430278:A:T	F130L	0.998
14:54430280:A:G	F130L	0.998
14:54430288:A:G	L127P	0.998
14:54430304:T:C	K122E	0.998
14:54430313:C:G	G119R	0.998
14:54430313:C:T	G119R	0.998
14:54430333:A:G	L112P	0.998
14:54430363:T:A	D102V	0.998
14:54430363:T:C	D102G	0.998
14:54430372:C:T	G99E	0.998
14:54432121:A:C	Y84D	0.998
14:54436385:C:A	C45F	0.998
14:54436386:A:G	C45R	0.998
14:54436399:A:C	N40K	0.998
14:54436399:A:T	N40K	0.998
14:54436421:T:A	E33V	0.998
14:54436422:C:T	E33K	0.998

dbSNP variants (sampled 300 via entrez): RS1000041847 (14:54439549 T>A,C), RS1000297023 (14:54433112 T>C,G), RS1000343156 (14:54427329 C>T), RS1000395949 (14:54426193 A>T), RS1000407415 (14:54426516 C>T), RS1000580827 (14:54434273 C>A,T), RS1000928835 (14:54439559 TTTG>T), RS1000992913 (14:54426561 C>A), RS1001034923 (14:54434503 C>T), RS1001097433 (14:54433696 A>G), RS1001650555 (14:54438918 C>A), RS1001750454 (14:54432661 T>G), RS1001800544 (14:54431035 G>A,C), RS1001901315 (14:54440075 T>C), RS1002014853 (14:54427103 C>T)

Disease associations

OMIM: gene MIM:611287 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST001786_22	Dental caries	2.000000e-07
GCST001786_33	Dental caries	2.000000e-06
GCST003477_3	Monobrow thickness	4.000000e-07

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

31 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	affects expression, increases abundance, decreases expression	3
sodium arsenite	increases abundance, increases expression	2
dicrotophos	decreases expression	1
bisphenol A	affects expression	1
deoxynivalenol	decreases expression	1
kojic acid	increases expression	1
beta-lapachone	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
cobaltous chloride	increases expression	1
nivalenol	decreases expression	1
beta-methylcholine	affects expression	1
chloropicrin	increases expression	1
K 7174	increases expression	1
ICG 001	decreases expression	1
nabiximols	increases expression	1
Air Pollutants, Occupational	affects expression	1
Arsenic	increases abundance, increases expression	1
Coal	decreases expression, increases abundance	1
Doxorubicin	decreases expression	1
Lead	increases expression	1
Ozone	affects expression, increases abundance	1
Selenium	decreases expression	1
Smoke	decreases expression, increases abundance	1
Tetrachlorodibenzodioxin	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	decreases expression	1
Valproic Acid	increases expression	1
Asbestos, Crocidolite	increases expression	1
Antirheumatic Agents	decreases expression	1
Copper Sulfate	decreases expression	1

Clinical trials (associated diseases)

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