C3orf52

Summary

C3orf52 (chromosome 3 open reading frame 52, HGNC:26255) is a protein-coding gene on chromosome 3q13.2, encoding TPA-induced transmembrane protein (Q5BVD1). Has a role in LIPH-mediated synthesis of 2-acyl lysophosphatidic acid (LPA).

Located in plasma membrane. Implicated in hypotrichosis 15.

Source: NCBI Gene 79669 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hypotrichosis 15 (Strong, GenCC)
• GWAS associations: 2
• Clinical variants (ClinVar): 57 total — 4 pathogenic
• Phenotypes (HPO): 2
• MANE Select transcript: NM_024616

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26255
Approved symbol	C3orf52
Name	chromosome 3 open reading frame 52
Location	3q13.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ23186, TTMP
Ensembl gene	ENSG00000114529
Ensembl biotype	protein_coding
OMIM	611956
Entrez	79669

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 5 protein_coding, 2 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000264848, ENST00000431717, ENST00000467942, ENST00000480282, ENST00000484828, ENST00000494096, ENST00000497610, ENST00000927376

RefSeq mRNA: 2 — MANE Select: NM_024616 NM_001171747, NM_024616

CCDS: CCDS46887, CCDS54620

Canonical transcript exons

ENST00000264848 — 6 exons

Exon	Start	End
ENSE00001200249	112109543	112109613
ENSE00001616166	112116642	112118210
ENSE00001815437	112086389	112086545
ENSE00003560490	112102838	112102965
ENSE00003567943	112093360	112093489
ENSE00003613660	112112964	112113145

Expression profiles

Bgee: expression breadth ubiquitous, 131 present calls, max score 93.22.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.6974 / max 348.4216, expressed in 1329 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
37917	5.7384	1251
37918	1.2305	563
37916	0.5392	328
37919	0.1893	86

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
skin of leg	UBERON:0001511	93.22	gold quality
zone of skin	UBERON:0000014	93.15	gold quality
skin of abdomen	UBERON:0001416	93.02	gold quality
body of pancreas	UBERON:0001150	91.53	gold quality
pancreas	UBERON:0001264	89.15	gold quality
rectum	UBERON:0001052	88.01	gold quality
islet of Langerhans	UBERON:0000006	85.34	gold quality
mucosa of transverse colon	UBERON:0004991	83.52	gold quality
thyroid gland	UBERON:0002046	82.34	gold quality
left lobe of thyroid gland	UBERON:0001120	82.32	gold quality
colonic epithelium	UBERON:0000397	81.90	gold quality
body of stomach	UBERON:0001161	81.69	gold quality
stomach	UBERON:0000945	80.87	gold quality
right lobe of thyroid gland	UBERON:0001119	80.57	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.96	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	79.39	gold quality
duodenum	UBERON:0002114	78.06	gold quality
upper lobe of left lung	UBERON:0008952	77.07	gold quality
placenta	UBERON:0001987	77.03	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	76.70	gold quality
transverse colon	UBERON:0001157	76.69	gold quality
gall bladder	UBERON:0002110	76.54	gold quality
fundus of stomach	UBERON:0001160	75.64	gold quality
lung	UBERON:0002048	75.53	gold quality
minor salivary gland	UBERON:0001830	75.41	gold quality
saliva-secreting gland	UBERON:0001044	74.86	gold quality
metanephros cortex	UBERON:0010533	74.74	gold quality
adult mammalian kidney	UBERON:0000082	74.24	gold quality
kidney	UBERON:0002113	74.00	gold quality
right lung	UBERON:0002167	73.37	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	10.15

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

64 targeting C3orf52, 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-513A-5P	100.00	69.77	2465
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-6744-5P	99.93	66.82	748
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-544A	99.84	68.66	1965
HSA-MIR-1323	99.83	69.89	2471
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-548AJ-5P	99.78	71.12	3085
HSA-MIR-548F-5P	99.78	71.02	3093
HSA-MIR-548G-5P	99.78	71.12	3085
HSA-MIR-548X-5P	99.78	71.12	3085
HSA-MIR-548O-3P	99.74	69.30	2228
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-1283	99.69	72.42	3009
HSA-MIR-4762-5P	99.57	68.54	1424

Literature-anchored findings (GeneRIF, showing 2)

• Loss-of-function variants in C3ORF52 result in localized autosomal recessive hypotrichosis. (PMID:32336749)
• A novel homozygous frameshift variant in the C3orf52 gene underlying isolated hair loss in a consanguineous family. (PMID:34309526)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	BC016579	ENSMUSG00000033187
rattus_norvegicus	C11h3orf52	ENSRNOG00000022136

Protein

Protein identifiers

TPA-induced transmembrane protein — Q5BVD1 (reviewed: Q5BVD1)

All UniProt accessions (2): H7C5J7, Q5BVD1

UniProt curated annotations — full annotation on UniProt →

Function. Has a role in LIPH-mediated synthesis of 2-acyl lysophosphatidic acid (LPA). LPA is a bioactive lipid mediator involved in different biological processes, and necessary to promote hair formation and growth.

Subunit / interactions. Interacts with LIPH.

Subcellular location. Endoplasmic reticulum. Cell membrane.

Tissue specificity. Detected predominantly in the skin, with strongest expression in the inner root sheath of the hair follicle.

Disease relevance. Hypotrichosis 15 (HYPT15) [MIM:620177] A form of hypotrichosis, a condition characterized by the presence of less than the normal amount of hair and abnormal hair follicles and shafts, which are thin and atrophic. The extent of scalp and body hair involvement can be very variable, within as well as between families. HYPT15 is an autosomal recessive form characterized by sparse to absent scalp and body hair. Eyebrows and eyelashes may be sparse or absent as well. The disease is caused by variants affecting the gene represented in this entry.

Induction. Up-regulated following treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA) in the pancreatic cancer cell line HPAF-II. The up-regulation by TPA is triggered at the promoter level.

Isoforms (3)

UniProt ID	Names	Canonical?
Q5BVD1-1	1	yes
Q5BVD1-2	2
Q5BVD1-3	3

RefSeq proteins (2): NP_001165218, NP_078892* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR033223	TTMP	Family

UniProt features (12 total): sequence variant 5, sequence conflict 2, splice variant 2, chain 1, transmembrane region 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5BVD1-F1	76.14	0.42

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 130 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_UP, GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_UP, NAGASHIMA_NRG1_SIGNALING_UP, ACEVEDO_LIVER_CANCER_WITH_H3K27ME3_UP, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM1, AMIT_SERUM_RESPONSE_120_MCF10A, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_DN, LEE_DOUBLE_POLAR_THYMOCYTE, MANALO_HYPOXIA_DN, CASORELLI_ACUTE_PROMYELOCYTIC_LEUKEMIA_DN, CHEN_METABOLIC_SYNDROM_NETWORK, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_WITH_LMP1_UP, ZHANG_RESPONSE_TO_IKK_INHIBITOR_AND_TNF_UP, WAMUNYOKOLI_OVARIAN_CANCER_LMP_UP, MIKKELSEN_ES_ICP_WITH_H3K4ME3

GO Biological Process (0):

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

GO Cellular Component (3): endoplasmic reticulum (GO:0005783), plasma membrane (GO:0005886), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

430 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
C3orf52	C16orf90	A8MZG2	474
C3orf52	SLITRK1	Q96PX8	446
C3orf52	LIPH	Q8WWY8	434
C3orf52	PGCKA1	Q8IY42	417
C3orf52	CLVS2	Q5SYC1	408
C3orf52	ZNF343	Q6P1L6	400
C3orf52	EIF3CL	B5ME19	373
C3orf52	SLC22A24	Q8N4F4	372
C3orf52	TMPRSS7	Q7RTY8	371
C3orf52	TMEM200A	Q86VY9	367
C3orf52	C19orf33	Q9GZP8	350
C3orf52	CMSS1	Q9BQ75	337
C3orf52	BMP10	O95393	327
C3orf52	GUCA1C	O95843	323
C3orf52	OGFRL1	Q5TC84	323

IntAct

230 interactions, top by confidence:

A	B	Type	Score
SGTA	TTMP	psi-mi:“MI:0915”(physical association)	0.720
TTMP	SGTA	psi-mi:“MI:0915”(physical association)	0.720
TTMP	TMX2	psi-mi:“MI:0915”(physical association)	0.670
TTMP	SIGLECL1	psi-mi:“MI:0915”(physical association)	0.670
TMPRSS2	TTMP	psi-mi:“MI:0915”(physical association)	0.630
SYNE4	TTMP	psi-mi:“MI:0915”(physical association)	0.560
TTMP	SYNE4	psi-mi:“MI:0915”(physical association)	0.560
TTMP	TMEM80	psi-mi:“MI:0915”(physical association)	0.560
TTMP	MGST2	psi-mi:“MI:0915”(physical association)	0.560
TTMP	ESAM	psi-mi:“MI:0915”(physical association)	0.560
TTMP	NEMP1	psi-mi:“MI:0915”(physical association)	0.560
TTMP	PVR	psi-mi:“MI:0915”(physical association)	0.560
TTMP	ZNRF3	psi-mi:“MI:0915”(physical association)	0.560
TTMP	CLDN7	psi-mi:“MI:0915”(physical association)	0.560
TTMP	LHFPL5	psi-mi:“MI:0915”(physical association)	0.560
TTMP	FFAR2	psi-mi:“MI:0915”(physical association)	0.560
TTMP	TMEM179B	psi-mi:“MI:0915”(physical association)	0.560
TTMP	RNF150	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (317): C3orf52 (Two-hybrid), SYNE4 (Two-hybrid), C3orf52 (Affinity Capture-MS), C3orf52 (Two-hybrid), C3orf52 (Affinity Capture-MS), C3orf52 (Affinity Capture-MS), C3orf52 (Affinity Capture-MS), C3orf52 (Affinity Capture-MS), C3orf52 (Affinity Capture-MS), C3orf52 (Affinity Capture-MS), C3orf52 (Affinity Capture-MS), C3orf52 (Two-hybrid), C3orf52 (Two-hybrid), C3orf52 (Two-hybrid), C3orf52 (Two-hybrid)

ESM2 similar proteins: A0A8M9PDM1, B8JI67, D3YX43, D5K8A9, E9Q8Q8, F1LW30, O70535, O95256, O95727, P20352, P27931, P42703, P43303, Q05928, Q0VCB1, Q14956, Q149L7, Q2YDG7, Q3SXY7, Q5BVD1, Q5U462, Q6AXW8, Q6AY06, Q6GMZ9, Q6P7C7, Q6P7N7, Q6PHB0, Q6PNM1, Q6UXZ4, Q7Z6A9, Q80VH0, Q8C4Q9, Q8C5C9, Q8IYV9, Q8K1S2, Q8K4B4, Q8NDB2, Q8NEA5, Q8QHJ9, Q90VY2

Diamond homologs: Q5BVD1, Q8C5C9

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 69 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
Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell	7	16.1×	2e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	0
Uncertain significance	31
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
1806468	NM_024616.3(C3orf52):c.492T>A (p.Tyr164Ter)	Pathogenic
1806469	NM_024616.3(C3orf52):c.34G>T (p.Glu12Ter)	Pathogenic
1806470	NM_024616.3(C3orf52):c.438_442del (p.Thr148fs)	Pathogenic
3776195	NM_024616.3(C3orf52):c.411C>G (p.Tyr137Ter)	Pathogenic

SpliceAI

1696 predictions. Top by Δscore:

Variant	Effect	Δscore
3:112086528:G:GT	donor_gain	1.0000
3:112086542:CGAG:C	donor_loss	1.0000
3:112086546:G:C	donor_loss	1.0000
3:112102834:TTAGT:T	acceptor_loss	1.0000
3:112102836:A:AG	acceptor_gain	1.0000
3:112102837:G:GT	acceptor_gain	1.0000
3:112102837:GT:G	acceptor_gain	1.0000
3:112102837:GTA:G	acceptor_gain	1.0000
3:112102837:GTAA:G	acceptor_gain	1.0000
3:112102837:GTAAC:G	acceptor_gain	1.0000
3:112102964:GG:G	donor_gain	1.0000
3:112102965:GG:G	donor_gain	1.0000
3:112112962:A:AG	acceptor_gain	1.0000
3:112112962:AGT:A	acceptor_gain	1.0000
3:112112963:G:GG	acceptor_gain	1.0000
3:112112963:GT:G	acceptor_gain	1.0000
3:112112963:GTG:G	acceptor_gain	1.0000
3:112112963:GTGGT:G	acceptor_gain	1.0000
3:112113145:GGTA:G	donor_loss	1.0000
3:112113146:G:C	donor_loss	1.0000
3:112113147:T:A	donor_loss	1.0000
3:112116639:TAG:T	acceptor_loss	1.0000
3:112116640:A:AG	acceptor_gain	1.0000
3:112116641:G:GG	acceptor_gain	1.0000
3:112116641:G:GT	acceptor_loss	1.0000
3:112116641:GA:G	acceptor_gain	1.0000
3:112116641:GAAT:G	acceptor_gain	1.0000
3:112126980:GACTT:G	donor_loss	1.0000
3:112126981:ACTT:A	donor_loss	1.0000
3:112126982:CTTAC:C	donor_loss	1.0000

AlphaMissense

1424 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:112112998:T:C	F168L	0.984
3:112113000:T:A	F168L	0.984
3:112113000:T:G	F168L	0.984
3:112109585:T:C	F147L	0.976
3:112109587:T:A	F147L	0.976
3:112109587:T:G	F147L	0.976
3:112112999:T:G	F168C	0.969
3:112112986:T:G	Y164D	0.966
3:112112993:T:C	L166P	0.966
3:112112999:T:C	F168S	0.963
3:112102894:T:C	F109L	0.961
3:112102896:C:A	F109L	0.961
3:112102896:C:G	F109L	0.961
3:112109586:T:C	F147S	0.961
3:112109555:T:G	Y137D	0.959
3:112109586:T:G	F147C	0.948
3:112112993:T:A	L166Q	0.939
3:112093447:G:C	G76R	0.930
3:112109544:T:A	L133H	0.920
3:112109544:T:C	L133P	0.919
3:112093420:T:A	W67R	0.918
3:112093420:T:C	W67R	0.918
3:112112993:T:G	L166R	0.914
3:112112986:T:A	Y164N	0.909
3:112102924:T:C	C119R	0.907
3:112109556:A:C	Y137S	0.902
3:112109555:T:A	Y137N	0.892
3:112102907:T:C	L113P	0.885
3:112112986:T:C	Y164H	0.883
3:112113103:T:A	C203S	0.883

dbSNP variants (sampled 300 via entrez): RS1000188231 (3:112098757 C>T), RS1000197956 (3:112098585 T>C), RS1000217342 (3:112101297 G>A), RS1000308416 (3:112091864 C>T), RS1000387689 (3:112086401 C>T), RS1000398201 (3:112119189 C>A,T), RS1000438727 (3:112086241 G>A), RS1000493452 (3:112128752 A>G), RS1000517943 (3:112124539 C>G,T), RS1000521672 (3:112115698 C>T), RS1000542094 (3:112097068 T>C), RS1000624320 (3:112134111 C>A,T), RS1000627903 (3:112125876 A>T), RS1000656944 (3:112133715 T>C), RS1000723686 (3:112085114 C>T)

Disease associations

OMIM: gene MIM:611956 | disease phenotypes: MIM:620177

GenCC curated gene-disease

Disease	Classification	Inheritance
hypotrichosis 15	Strong	Autosomal recessive

Mondo (1): hypotrichosis 15 (MONDO:0859341)

Orphanet (0):

HPO phenotypes

2 total (2 of 2 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0002209	Sparse scalp hair

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST90002381_179	Eosinophil count	2.000000e-14
GCST90002382_574	Eosinophil percentage of white cells	2.000000e-13

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004842	eosinophil count
EFO:0007991	eosinophil percentage of leukocytes

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	7
Benzo(a)pyrene	affects methylation, increases expression	6
Aflatoxin B1	affects expression, increases expression	5
trichostatin A	increases expression, affects cotreatment	3
Cyclosporine	decreases expression, increases expression	3
sodium arsenite	increases expression, decreases expression, increases abundance	2
entinostat	increases expression, affects cotreatment	2
Vorinostat	affects cotreatment, increases expression	2
Panobinostat	affects cotreatment, increases expression	2
Lipopolysaccharides	decreases reaction, affects cotreatment, decreases expression, increases expression	2
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
2-methyl-4-isothiazolin-3-one	increases expression	1
butyraldehyde	increases expression	1
S-(1,2-dichlorovinyl)cysteine	decreases reaction, increases expression	1
diallyl trisulfide	increases expression	1
pentanal	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
erucylphospho-N,N,N-trimethylpropylammonium	increases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Temozolomide	decreases expression	1
Sunitinib	increases expression	1
Arsenic	decreases expression, increases abundance	1
Cisplatin	increases expression	1
Copper	affects binding, decreases expression	1
Coumestrol	decreases expression	1
Diethylhexyl Phthalate	increases expression	1
Disulfiram	affects binding, decreases expression	1

Clinical trials (associated diseases)

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