CLMB

Summary

CLMB (calcimembrin, HGNC:23362) is a protein-coding gene on chromosome 16q24.1, encoding Uncharacterized protein C16orf74 (Q96GX8).

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 18 total — 3 pathogenic
• MANE Select transcript: NM_206967

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23362
Approved symbol	CLMB
Name	calcimembrin
Location	16q24.1
Locus type	gene with protein product
Status	Approved
Aliases	MGC17624, MICT1
Ensembl gene	ENSG00000154102
Ensembl biotype	protein_coding
Entrez	404550

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 6 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000284245, ENST00000602583, ENST00000602675, ENST00000602719, ENST00000602758, ENST00000602766, ENST00000602914

RefSeq mRNA: 1 — MANE Select: NM_206967 NM_206967

CCDS: CCDS45540

Canonical transcript exons

ENST00000284245 — 4 exons

Exon	Start	End
ENSE00001014066	85710164	85710307
ENSE00001330299	85707517	85708066
ENSE00001530914	85750926	85751096
ENSE00003672688	85735190	85735235

Expression profiles

Bgee: expression breadth ubiquitous, 163 present calls, max score 92.61.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.2959 / max 192.9324, expressed in 1425 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
158410	9.9063	1394
158412	0.8401	387
158411	0.2691	142
158409	0.2044	111
158404	0.0760	20

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	92.61	gold quality
secondary oocyte	CL:0000655	89.99	gold quality
lower esophagus mucosa	UBERON:0035834	87.36	gold quality
bone marrow cell	CL:0002092	82.49	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	82.02	gold quality
spleen	UBERON:0002106	81.68	gold quality
granulocyte	CL:0000094	81.24	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.57	gold quality
monocyte	CL:0000576	79.33	gold quality
leukocyte	CL:0000738	79.32	gold quality
stromal cell of endometrium	CL:0002255	78.64	gold quality
upper arm skin	UBERON:0004263	77.78	gold quality
esophagus mucosa	UBERON:0002469	76.52	gold quality
skin of abdomen	UBERON:0001416	76.18	gold quality
kidney epithelium	UBERON:0004819	76.18	gold quality
ventricular zone	UBERON:0003053	76.17	gold quality
vagina	UBERON:0000996	75.78	gold quality
bone marrow	UBERON:0002371	75.64	gold quality
amygdala	UBERON:0001876	75.16	gold quality
nasal cavity mucosa	UBERON:0001826	74.88	gold quality
placenta	UBERON:0001987	74.83	gold quality
skin of leg	UBERON:0001511	74.69	gold quality
cerebellar vermis	UBERON:0004720	74.65	gold quality
lymph node	UBERON:0000029	74.61	gold quality
blood	UBERON:0000178	74.56	gold quality
ectocervix	UBERON:0012249	74.43	gold quality
urinary bladder	UBERON:0001255	74.23	gold quality
zone of skin	UBERON:0000014	73.66	gold quality
pigmented layer of retina	UBERON:0001782	72.67	gold quality
apex of heart	UBERON:0002098	72.57	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-MTAB-10855	yes	172.74
E-CURD-114	yes	69.35
E-HCAD-4	yes	57.06
E-ANND-3	yes	10.24
E-MTAB-10553	yes	8.14
E-MTAB-8410	no	0.95

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

22 targeting CLMB, 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-3613-3P	100.00	76.36	7965
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-6817-3P	99.79	68.35	2126
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-1299	99.77	71.24	2389
HSA-MIR-5700	99.64	69.88	2280
HSA-MIR-148A-5P	99.30	68.27	1141
HSA-MIR-5584-3P	99.23	68.79	1351
HSA-MIR-605-5P	98.79	68.24	1161
HSA-MIR-198	98.70	67.32	920
HSA-MIR-7850-5P	98.12	67.28	1111
HSA-MIR-3194-5P	96.80	64.90	1027
HSA-MIR-1269A	92.75	64.61	542
HSA-MIR-1269B	92.75	64.73	538

Literature-anchored findings (GeneRIF, showing 3)

• C16orf74 expression level represents a potentially useful marker for predicting progression in primary non-muscle invasive bladder cancer patients (PMID:21203532)
• Role of Dimerized C16orf74 in Aggressive Pancreatic Cancer: A Novel Therapeutic Target. (PMID:31597713)
• LncRNA HAND2-AS1 represses cervical cancer progression by interaction with transcription factor E2F4 at the promoter of C16orf74. (PMID:32314545)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	1190005I06Rik	ENSMUSG00000043687
rattus_norvegicus	C19h16orf74	ENSRNOG00000017646

Protein

Protein identifiers

Uncharacterized protein C16orf74 — Q96GX8 (reviewed: Q96GX8)

All UniProt accessions (5): Q96GX8, A0A0M5MPK6, R4GMV5, R4GMY0, R4GNJ3

UniProt curated annotations — full annotation on UniProt →

Subunit / interactions. Interacts (via PxIxIT motif, when phosphorylated on Thr-44) with PPP3CA.

Tissue specificity. Not expressed in pancreatic duct cells (at protein level). Abundantly expressed in the pancreas and weakly expressed in the thyroid. Not expressed in pancreatic duct cells (at protein level). Abundantly expressed in the lymph node and weakly expressed in the stomach, trachea and bone marrow.

Miscellaneous. May act as a prognostic marker of median survival time in pancreatic cancer patients.

Isoforms (2)

UniProt ID	Names	Canonical?
Q96GX8-1	1, V1	yes
Q96GX8-2	2, V3

RefSeq proteins (1): NP_996850* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR027864	DUF4597	Family

Pfam: PF15366

UniProt features (8 total): mutagenesis site 3, modified residue 2, chain 1, region of interest 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96GX8-F1	68.83	0.01

Functional residue map

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

Post-translational modifications (2): 44, 46

Mutagenesis-validated functional residues (3):

Position	Phenotype
36–41	abolishes interaction with ppp3ca.
41	no effect on phosphorylation.
44	abolished phosphorylation and interaction with ppp3ca.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 78 (showing top): GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, NIKOLSKY_BREAST_CANCER_16Q24_AMPLICON, NKX22_01, BURTON_ADIPOGENESIS_5, PITX2_Q2, SARTIPY_NORMAL_AT_INSULIN_RESISTANCE_DN, SENESE_HDAC3_TARGETS_DN, TGGAAA_NFAT_Q4_01, MEISSNER_NPC_HCP_WITH_H3K4ME2, BHAT_ESR1_TARGETS_NOT_VIA_AKT1_UP, BHAT_ESR1_TARGETS_VIA_AKT1_UP, BRUINS_UVC_RESPONSE_LATE, E2F3_UP.V1_DN, MYC_UP.V1_DN

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

218 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CLMB	EMC8	O43402	626
CLMB	GINS2	Q9Y248	509
CLMB	C3orf80	F5H4A9	503
CLMB	COX4I1	P13073	421
CLMB	CCER2	I3L3R5	417
CLMB	EID2B	Q96D98	374
CLMB	A8MSY1	A8MSY1	358
CLMB	EMC1	Q8N766	350
CLMB	TNS4	Q8IZW8	344
CLMB	LIX1L	Q8IVB5	324
CLMB	ANXA10	Q9UJ72	319
CLMB	SACK1A	Q86UY5	316
CLMB	ZNG1A	Q9BRT8	311
CLMB	HSF5	Q4G112	305
CLMB	DSEL	Q8IZU8	302

IntAct

16 interactions, top by confidence:

A	B	Type	Score
C16orf74	UNC119	psi-mi:“MI:0915”(physical association)	0.780
UNC119	C16orf74	psi-mi:“MI:0915”(physical association)	0.780
PPP3CA	C16orf74	psi-mi:“MI:0915”(physical association)	0.670
C16orf74	PPP3CA	psi-mi:“MI:0915”(physical association)	0.670
PPP3CA	C16orf74	psi-mi:“MI:0915”(physical association)	0.560
C16orf74	PPP3CC	psi-mi:“MI:0914”(association)	0.350
PPP3CA	C16orf74	psi-mi:“MI:0915”(physical association)	0.000
UNC119	C16orf74	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (11): C16orf74 (Two-hybrid), C16orf74 (Two-hybrid), C16orf74 (Two-hybrid), C16orf74 (Two-hybrid), PPP3CA (Two-hybrid), C16orf74 (Two-hybrid), C16orf74 (Two-hybrid), PPP3CC (Affinity Capture-MS), ZER1 (Affinity Capture-MS), ADO (Affinity Capture-MS), KLHL20 (Affinity Capture-MS)

ESM2 similar proteins: A0A7P0TBJ1, A4IG66, A8E4V2, B8AE37, O55003, O60238, O70239, O94876, P02683, P42857, P58821, Q02225, Q08DP3, Q0VA20, Q12983, Q3T013, Q4QQM5, Q4R5Q3, Q503U3, Q5F3A4, Q5M836, Q5RF46, Q5XG16, Q62092, Q68EF0, Q6DD53, Q6GQI8, Q6GR21, Q6K678, Q6ZPJ0, Q7TMB7, Q7Z2D5, Q7Z3D4, Q8AVJ1, Q8BHS8, Q8BPM6, Q8GYL9, Q8GZ92, Q8IUW5, Q8IWB9

Diamond homologs: Q8K1L6, Q96GX8

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	0
Uncertain significance	7
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
2685585	GRCh37/hg19 16q24.1-24.2(chr16:84555718-87910245)x1	Pathogenic
443397	GRCh37/hg19 16q24.1-24.2(chr16:85491404-87883528)x1	Pathogenic
625611	GRCh37/hg19 16q23.3-24.3(chr16:82761333-90055381)	Pathogenic

SpliceAI

948 predictions. Top by Δscore:

Variant	Effect	Δscore
16:85750922:TCA:T	donor_loss	1.0000
16:85750924:A:AC	donor_gain	1.0000
16:85750925:C:CC	donor_gain	1.0000
16:85750925:CCG:C	donor_gain	1.0000
16:85750930:T:TA	donor_gain	1.0000
16:85710339:G:C	acceptor_gain	0.9900
16:85735184:CCTTA:C	donor_loss	0.9900
16:85735187:TA:T	donor_loss	0.9900
16:85750924:ACCG:A	donor_gain	0.9900
16:85750925:CCGC:C	donor_gain	0.9900
16:85750925:CCGCT:C	donor_gain	0.9900
16:85708062:CCAGA:C	acceptor_gain	0.9800
16:85708063:CAGA:C	acceptor_gain	0.9800
16:85708063:CAGAC:C	acceptor_gain	0.9800
16:85708067:C:CC	acceptor_gain	0.9800
16:85710477:A:T	acceptor_gain	0.9800
16:85750924:AC:A	donor_gain	0.9800
16:85750925:CC:C	donor_gain	0.9800
16:85710321:C:CT	acceptor_gain	0.9700
16:85710336:CACG:C	acceptor_gain	0.9700
16:85710338:CG:C	acceptor_gain	0.9700
16:85710342:C:CT	acceptor_gain	0.9700
16:85710317:C:CT	acceptor_gain	0.9600
16:85710334:C:CT	acceptor_gain	0.9600
16:85710476:C:CT	acceptor_gain	0.9600
16:85735183:GCCTT:G	donor_loss	0.9600
16:85735236:C:CC	acceptor_gain	0.9600
16:85708064:AGA:A	acceptor_gain	0.9500
16:85708065:GA:G	acceptor_gain	0.9500
16:85710515:C:CT	acceptor_gain	0.9500

AlphaMissense

512 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:85710223:A:C	I38S	0.988
16:85710223:A:G	I38T	0.986
16:85710217:A:T	I40N	0.983
16:85710208:G:T	P43H	0.982
16:85710217:A:C	I40S	0.980
16:85710223:A:T	I38N	0.980
16:85710211:G:T	P42H	0.978
16:85710220:A:C	I39S	0.971
16:85710220:A:T	I39N	0.968
16:85710230:G:A	P36S	0.968
16:85710209:G:A	P43S	0.967
16:85710229:G:T	P36H	0.967
16:85710211:G:C	P42R	0.965
16:85710212:G:A	P42S	0.965
16:85710214:G:T	T41K	0.965
16:85710208:G:C	P43R	0.964
16:85710209:G:T	P43T	0.963
16:85710212:G:T	P42T	0.961
16:85710230:G:T	P36T	0.959
16:85710214:G:C	T41R	0.955
16:85710217:A:G	I40T	0.955
16:85710205:G:T	T44N	0.945
16:85735199:A:G	C7R	0.945
16:85710229:G:C	P36R	0.939
16:85710202:G:T	P45H	0.937
16:85710229:G:A	P36L	0.935
16:85735197:G:C	C7W	0.933
16:85710208:G:A	P43L	0.931
16:85710294:A:C	C14W	0.931
16:85710232:A:T	V35E	0.927

dbSNP variants (sampled 300 via entrez): RS1000026284 (16:85720691 G>A,C), RS1000037634 (16:85725390 T>C), RS1000063495 (16:85747952 G>A), RS1000093546 (16:85720968 G>A,C), RS1000106073 (16:85724669 G>C), RS1000122926 (16:85750920 A>C,G), RS1000228473 (16:85708937 C>A,G,T), RS1000237646 (16:85750778 C>A), RS1000337657 (16:85728130 T>C), RS1000344016 (16:85712793 C>G,T), RS1000455968 (16:85750271 G>C), RS1000516157 (16:85709871 T>C), RS1000554317 (16:85748454 C>T), RS1000569355 (16:85736614 C>A,G), RS1000591355 (16:85736791 C>G,T)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST002337_16	Amyotrophic lateral sclerosis (sporadic)	2.000000e-06
GCST003400_21	Type 2 diabetes	6.000000e-07

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases expression, affects methylation, decreases methylation	2
triphenyl phosphate	affects expression	1
bisphenol A	decreases methylation	1
beta-lapachone	increases expression	1
arsenite	affects binding, increases reaction	1
sodium arsenite	decreases expression	1
cobaltous chloride	decreases expression	1
benzo(e)pyrene	increases methylation	1
hydroquinone	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression	1
clothianidin	decreases expression	1
abrine	decreases expression	1
bisphenol S	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Amiodarone	increases expression	1
Cisplatin	increases expression, affects cotreatment	1
Dimethyl Sulfoxide	affects expression	1
Formaldehyde	increases expression	1
Lipopolysaccharides	decreases expression, affects cotreatment	1
Methapyrilene	increases methylation	1
Methylcholanthrene	affects binding, increases reaction	1
Smoke	decreases expression	1
Tetrachlorodibenzodioxin	affects expression	1
Tobacco Smoke Pollution	affects expression	1
Valproic Acid	increases methylation	1
Aflatoxin B1	increases methylation	1
Acrylamide	increases expression	1

Clinical trials (associated diseases)

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