C18orf32

Summary

C18orf32 (chromosome 18 open reading frame 32, HGNC:31690) is a protein-coding gene on chromosome 18q21.1, encoding UPF0729 protein C18orf32 (Q8TCD1). May activate the NF-kappa-B signaling pathway.

Involved in positive regulation of canonical NF-kappaB signal transduction. Located in endoplasmic reticulum and lipid droplet.

Source: NCBI Gene 497661 — RefSeq curated summary.

At a glance

• Gene–disease (curated): glycosylphosphatidylinositol biosynthesis defect 25 (Limited, GenCC)
• Clinical variants (ClinVar): 3 total
• Phenotypes (HPO): 12
• MANE Select transcript: NM_001035005

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:31690
Approved symbol	C18orf32
Name	chromosome 18 open reading frame 32
Location	18q21.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ23458
Ensembl gene	ENSG00000177576
Ensembl biotype	protein_coding
OMIM	619979
Entrez	497661

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 16 protein_coding

ENST00000318240, ENST00000582392, ENST00000613385, ENST00000851744, ENST00000851745, ENST00000851746, ENST00000851747, ENST00000851748, ENST00000851749, ENST00000851750, ENST00000918681, ENST00000918682, ENST00000918683, ENST00000918684, ENST00000950409, ENST00000950410

RefSeq mRNA: 2 — MANE Select: NM_001035005 NM_001035005, NM_001199346

CCDS: CCDS32831

Canonical transcript exons

ENST00000318240 — 3 exons

Exon	Start	End
ENSE00001238569	49477243	49482410
ENSE00001533687	49487043	49487234
ENSE00003728294	49483584	49483771

Expression profiles

Bgee: expression breadth ubiquitous, 133 present calls, max score 92.68.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 66.2574 / max 759.8381, expressed in 1820 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
171910	43.7198	1816
171909	18.5758	1780
171908	3.9619	1545

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	92.68	gold quality
leukocyte	CL:0000738	91.53	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	86.41	gold quality
endometrium	UBERON:0001295	86.19	gold quality
islet of Langerhans	UBERON:0000006	85.09	gold quality
substantia nigra	UBERON:0002038	83.12	gold quality
pancreas	UBERON:0001264	82.76	gold quality
body of pancreas	UBERON:0001150	82.71	gold quality
rectum	UBERON:0001052	82.62	gold quality
Ammon’s horn	UBERON:0001954	81.75	gold quality
corpus callosum	UBERON:0002336	81.58	gold quality
granulocyte	CL:0000094	81.42	gold quality
amygdala	UBERON:0001876	81.39	gold quality
temporal lobe	UBERON:0001871	81.25	gold quality
blood	UBERON:0000178	81.08	gold quality
cortical plate	UBERON:0005343	80.92	gold quality
putamen	UBERON:0001874	80.88	gold quality
smooth muscle tissue	UBERON:0001135	80.84	gold quality
anterior cingulate cortex	UBERON:0009835	80.74	gold quality
adrenal tissue	UBERON:0018303	80.58	gold quality
nucleus accumbens	UBERON:0001882	80.54	gold quality
Brodmann (1909) area 9	UBERON:0013540	80.50	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	80.45	gold quality
hypothalamus	UBERON:0001898	80.15	gold quality
caudate nucleus	UBERON:0001873	79.93	gold quality
cerebral cortex	UBERON:0000956	79.58	gold quality
brain	UBERON:0000955	79.56	gold quality
bone marrow cell	CL:0002092	79.07	gold quality
placenta	UBERON:0001987	79.02	gold quality
lymph node	UBERON:0000029	78.72	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	12.36

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

59 targeting C18orf32, 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-3646	100.00	73.56	5283
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-519D-3P	99.88	73.97	2607
HSA-MIR-526B-3P	99.88	74.06	2587
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-204-5P	99.79	71.62	2439
HSA-MIR-211-5P	99.79	71.65	2440
HSA-MIR-577	99.78	69.13	2479
HSA-MIR-4446-5P	99.72	69.19	2544
HSA-MIR-4755-5P	99.71	70.34	2716
HSA-MIR-5006-3P	99.71	70.26	2728
HSA-MIR-4756-3P	99.62	66.30	1319
HSA-MIR-5003-5P	99.61	69.13	1624
HSA-MIR-802	99.61	67.70	1254
HSA-MIR-4276	99.56	67.66	2514
HSA-MIR-3120-3P	99.54	70.28	2669
HSA-MIR-6832-3P	99.52	70.44	1726

Literature-anchored findings (GeneRIF, showing 1)

• C18orf32 loss-of-function is associated with a neurodevelopmental disorder with hypotonia and contractures. (PMID:35107634)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	BC031181	ENSMUSG00000036299
rattus_norvegicus	C18h18orf32	ENSRNOG00000018676

Protein

Protein identifiers

UPF0729 protein C18orf32 — Q8TCD1 (reviewed: Q8TCD1)

Alternative names: Putative NF-kappa-B-activating protein 200

All UniProt accessions (1): Q8TCD1

UniProt curated annotations — full annotation on UniProt →

Function. May activate the NF-kappa-B signaling pathway.

Subunit / interactions. Interacts with DERL1 and AMFR.

Subcellular location. Endoplasmic reticulum. Lipid droplet.

Post-translational modifications. Undergoes ER-associated degradation (ERAD).

Disease relevance. Glycosylphosphatidylinositol biosynthesis defect 25 (GPIBD25) [MIM:619985] An autosomal recessive disorder with onset in early infancy and characterized by global developmental delay with almost no milestone achievement, brain anomalies, hypotonia, and contractures. Death may occur in early childhood. The disease may be caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the UPF0729 family.

RefSeq proteins (2): NP_001030177, NP_001186275 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026776	UPF0729_C18orf32-like	Family

Pfam: PF14975

UniProt features (4 total): region of interest 2, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TCD1-F1	66.54	0.06

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 120 (showing top): GOBP_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, GOBP_POSITIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, GOBP_POSITIVE_REGULATION_OF_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, KRIGE_RESPONSE_TO_TOSEDOSTAT_24HR_UP, chr18q21, WANG_RESPONSE_TO_GSK3_INHIBITOR_SB216763_UP, PURBEY_TARGETS_OF_CTBP1_NOT_SATB1_DN, GOCC_LIPID_DROPLET, RB_DN.V1_DN, GSE13547_CTRL_VS_ANTI_IGM_STIM_BCELL_12H_DN, BARX1_TARGET_GENES, ELF2_TARGET_GENES, ID1_TARGET_GENES, SETD7_TARGET_GENES

GO Biological Process (1): positive regulation of canonical NF-kappaB signal transduction (GO:0043123)

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

GO Cellular Component (2): endoplasmic reticulum (GO:0005783), lipid droplet (GO:0005811)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
canonical NF-kappaB signal transduction	1
regulation of canonical NF-kappaB signal transduction	1
positive regulation of intracellular signal transduction	1
binding	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

256 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
C18orf32	OCIAD1	Q9NX40	496
C18orf32	NDUFS5	O43920	492
C18orf32	ATP5ME	P56385	486
C18orf32	UQCR10	Q9UDW1	482
C18orf32	RPL23A	P29316	479
C18orf32	UBAC2	Q8NBM4	475
C18orf32	NDUFA5	Q16718	471
C18orf32	RPS14	P06366	469
C18orf32	PHOSPHO2	Q8TCD6	446
C18orf32	ETFRF1	Q6IPR1	444
C18orf32	MPV17L2	Q567V2	437
C18orf32	CYB5B	O43169	426
C18orf32	MT-ND4	P03905	416
C18orf32	CLPTM1	O96005	414
C18orf32	A0A0A6YYL6	A0A0A6YYL6	407

IntAct

10 interactions, top by confidence:

A	B	Type	Score
C18orf32	GLP1R	psi-mi:“MI:0915”(physical association)	0.510
GLP1R	C18orf32	psi-mi:“MI:0915”(physical association)	0.510
C18orf32	SMO	psi-mi:“MI:0915”(physical association)	0.370
C18orf32	CACNA1C	psi-mi:“MI:0915”(physical association)	0.370
MAP1LC3A		psi-mi:“MI:0914”(association)	0.350
GABARAPL2		psi-mi:“MI:0914”(association)	0.350
GABARAPL1		psi-mi:“MI:0914”(association)	0.350
GABARAP		psi-mi:“MI:0914”(association)	0.350
TCTN2	TMEM120B	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (14): C18orf32 (Proximity Label-MS), C18orf32 (Proximity Label-MS), C18orf32 (Proximity Label-MS), C18orf32 (Proximity Label-MS), C18orf32 (Proximity Label-MS), C18orf32 (Two-hybrid), C18orf32 (Proximity Label-MS), C18orf32 (Proximity Label-MS), C18orf32 (Proximity Label-MS), C18orf32 (Two-hybrid), C18orf32 (Affinity Capture-MS), C18orf32 (Proximity Label-MS), C18orf32 (PCA), C18orf32 (Affinity Capture-Western)

ESM2 similar proteins: A8NJ91, A8WTH5, B1WC88, B3P5J1, B4GPI0, B4R3W7, C1BY38, C3KHG1, O01323, O54851, O70610, O77286, O97172, P0C8Y2, P0DKX4, P28236, P48165, P56695, Q05B71, Q15053, Q16EE5, Q28I13, Q29BX8, Q2KI30, Q2TBG9, Q3ZC78, Q5F3A1, Q5HZP8, Q5I027, Q5R4Q3, Q5R7A0, Q6AZM3, Q6NUK4, Q6P418, Q6PCF8, Q7PSY2, Q8AVX1, Q8BU14, Q8K4Q9, Q8N5K1

Diamond homologs: A8NJ91, A8WTH5, B1WC88, C1BY38, C3KHG1, O01323, O97172, P0C8Y2, Q16EE5, Q28I13, Q3ZC78, Q5R7A0, Q8TCD1, Q91WE4, B4R3W7, Q7PSY2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	3
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

564 predictions. Top by Δscore:

Variant	Effect	Δscore
18:49482293:T:TA	donor_gain	1.0000
18:49482360:A:AC	donor_gain	1.0000
18:49482409:CC:C	acceptor_gain	1.0000
18:49482409:CCCTA:C	acceptor_loss	1.0000
18:49482410:CC:C	acceptor_gain	1.0000
18:49482410:CCTA:C	acceptor_loss	1.0000
18:49482411:CTAAA:C	acceptor_loss	1.0000
18:49483578:TCTTA:T	donor_loss	1.0000
18:49483579:CTTAC:C	donor_loss	1.0000
18:49483580:TTAC:T	donor_loss	1.0000
18:49483580:TTACC:T	donor_loss	1.0000
18:49483581:TA:T	donor_loss	1.0000
18:49483582:A:C	donor_loss	1.0000
18:49483583:C:A	donor_loss	1.0000
18:49483583:C:CG	donor_loss	1.0000
18:49483767:CTCAA:C	acceptor_gain	1.0000
18:49483769:CAA:C	acceptor_gain	1.0000
18:49483771:AC:A	acceptor_loss	1.0000
18:49483772:C:CA	acceptor_loss	1.0000
18:49483772:C:CC	acceptor_gain	1.0000
18:49483780:A:AC	acceptor_gain	1.0000
18:49483780:A:C	acceptor_gain	1.0000
18:49483782:A:AC	acceptor_gain	1.0000
18:49483782:A:C	acceptor_gain	1.0000
18:49487205:AC:A	donor_gain	1.0000
18:49487206:CC:C	donor_gain	1.0000
18:49482204:T:TA	donor_gain	0.9900
18:49482238:AT:A	donor_gain	0.9900
18:49482407:CACC:C	acceptor_gain	0.9900
18:49482411:C:CC	acceptor_gain	0.9900

AlphaMissense

499 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
18:49483720:G:T	P10Q	0.986
18:49483709:A:G	W14R	0.981
18:49483709:A:T	W14R	0.981
18:49483726:A:T	V8D	0.981
18:49483720:G:C	P10R	0.980
18:49483733:A:G	C6R	0.978
18:49483711:A:T	L13H	0.977
18:49483742:A:G	C3R	0.977
18:49483729:A:T	I7N	0.973
18:49483735:G:T	P5H	0.972
18:49483735:G:C	P5R	0.971
18:49483699:T:A	K17I	0.968
18:49483717:A:T	V11D	0.968
18:49483723:A:T	I9N	0.967
18:49483692:G:C	F19L	0.965
18:49483692:G:T	F19L	0.965
18:49483694:A:G	F19L	0.965
18:49483714:A:C	L12R	0.963
18:49483723:A:G	I9T	0.963
18:49483740:G:C	C3W	0.963
18:49483721:G:A	P10S	0.962
18:49483711:A:G	L13P	0.961
18:49483738:A:T	I4N	0.961
18:49483698:T:A	K17N	0.959
18:49483698:T:G	K17N	0.959
18:49483723:A:C	I9S	0.956
18:49483741:C:T	C3Y	0.955
18:49483731:A:C	C6W	0.952
18:49483745:C:T	V2M	0.951
18:49483732:C:T	C6Y	0.948

dbSNP variants (sampled 300 via entrez): RS1000015157 (18:49477751 G>A), RS1000167975 (18:49483504 T>C), RS1000193456 (18:49480563 G>A), RS1000261753 (18:49488623 G>A), RS1000314483 (18:49488255 A>T), RS1000460489 (18:49486700 T>C), RS1000599285 (18:49487575 T>C), RS1000651768 (18:49487383 C>T), RS1000712280 (18:49487322 G>A,T), RS1000747061 (18:49487426 T>C,G), RS1000831168 (18:49486469 C>G), RS1000906429 (18:49481970 C>T), RS1000977482 (18:49481809 C>T), RS1001228350 (18:49477364 G>A), RS1001264303 (18:49486775 G>C)

Disease associations

OMIM: gene MIM:619979 | disease phenotypes: MIM:619985

GenCC curated gene-disease

Disease	Classification	Inheritance
glycosylphosphatidylinositol biosynthesis defect 25	Limited	Autosomal recessive

Mondo (1): glycosylphosphatidylinositol biosynthesis defect 25 (MONDO:0859271)

Orphanet (0):

HPO phenotypes

12 total (12 of 12 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0001252	Hypotonia
HP:0002188	Delayed CNS myelination
HP:0002208	Coarse hair
HP:0003186	Inverted nipples
HP:0003282	Decreased circulating alkaline phosphatase activity
HP:0003577	Congenital onset
HP:0003819	Death in childhood
HP:0004322	Short stature
HP:0006466	Ankle flexion contracture
HP:0008070	Sparse hair
HP:0011344	Severe global developmental delay

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

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

Chemical	Actions (top 5)	PubMed papers
Tretinoin	affects cotreatment, decreases expression, increases expression	3
aristolochic acid I	increases expression	1
dicrotophos	decreases expression	1
bisphenol A	decreases expression	1
beta-lapachone	increases expression	1
sodium arsenite	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
K 7174	increases expression	1
Air Pollutants	affects expression, increases abundance	1
Benzo(a)pyrene	increases methylation	1
Coumestrol	decreases expression	1
Doxorubicin	decreases expression	1
Estradiol	decreases expression	1
Formaldehyde	increases expression	1
Oxygen	increases expression	1
Ozone	affects expression, increases abundance	1
Cyclosporine	increases expression	1
Aflatoxin B1	decreases expression	1

Clinical trials (associated diseases)

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