C2CD4D

Summary

C2CD4D (C2 calcium dependent domain containing 4D, HGNC:37210) is a protein-coding gene on chromosome 1q21.3, encoding C2 calcium-dependent domain-containing protein 4D (B7Z1M9).

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 80 total — 1 pathogenic
• MANE Select transcript: NM_001394591

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:37210
Approved symbol	C2CD4D
Name	C2 calcium dependent domain containing 4D
Location	1q21.3
Locus type	gene with protein product
Status	Approved
Aliases	FAM148D
Ensembl gene	ENSG00000225556
Ensembl biotype	protein_coding
Entrez	100191040

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 10 protein_coding

ENST00000454109, ENST00000694868, ENST00000694869, ENST00000851307, ENST00000851308, ENST00000851309, ENST00000851310, ENST00000851311, ENST00000851312, ENST00000923260

RefSeq mRNA: 4 — MANE Select: NM_001394591 NM_001136003, NM_001394591, NM_001394592, NM_001394593

CCDS: CCDS44224

Canonical transcript exons

ENST00000694868 — 2 exons

Exon	Start	End
ENSE00003961085	151839664	151839820
ENSE00003963216	151837818	151839220

Expression profiles

Bgee: expression breadth ubiquitous, 112 present calls, max score 66.34.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
skin of leg	UBERON:0001511	66.34	gold quality
zone of skin	UBERON:0000014	64.75	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	64.23	gold quality
skin of abdomen	UBERON:0001416	62.85	gold quality
superior frontal gyrus	UBERON:0002661	62.48	gold quality
primary visual cortex	UBERON:0002436	61.49	gold quality
sural nerve	UBERON:0015488	61.27	silver quality
prefrontal cortex	UBERON:0000451	60.47	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	60.40	gold quality
granulocyte	CL:0000094	59.85	gold quality
Brodmann (1909) area 9	UBERON:0013540	58.75	gold quality
frontal cortex	UBERON:0001870	57.92	gold quality
mucosa of transverse colon	UBERON:0004991	57.48	gold quality
bone marrow cell	CL:0002092	56.51	gold quality
saliva-secreting gland	UBERON:0001044	56.44	gold quality
cerebral cortex	UBERON:0000956	56.15	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	56.06	gold quality
minor salivary gland	UBERON:0001830	55.92	gold quality
adult mammalian kidney	UBERON:0000082	55.91	gold quality
substantia nigra	UBERON:0002038	55.75	gold quality
cerebellum	UBERON:0002037	55.18	gold quality
Ammon’s horn	UBERON:0001954	55.17	gold quality
right hemisphere of cerebellum	UBERON:0014890	55.14	gold quality
cortex of kidney	UBERON:0001225	55.08	gold quality
cerebellar cortex	UBERON:0002129	55.02	gold quality
cerebellar hemisphere	UBERON:0002245	54.77	gold quality
tonsil	UBERON:0002372	53.62	gold quality
right frontal lobe	UBERON:0002810	53.49	gold quality
lower esophagus mucosa	UBERON:0035834	53.45	gold quality
kidney	UBERON:0002113	53.37	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.43

Regulation

Is transcription factor: no

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	C2cd4d	ENSMUSG00000091648
rattus_norvegicus	C2cd4d	ENSRNOG00000020832

Paralogs (31): SYT7 (ENSG00000011347), SYT13 (ENSG00000019505), SYT1 (ENSG00000067715), RPH3A (ENSG00000089169), SYTL4 (ENSG00000102362), SYT17 (ENSG00000103528), SYT10 (ENSG00000110975), SYT5 (ENSG00000129990), SYT11 (ENSG00000132718), SYT4 (ENSG00000132872), SYT6 (ENSG00000134207), SYTL2 (ENSG00000137501), SYT16 (ENSG00000139973), SYTL1 (ENSG00000142765), SYT14 (ENSG00000143469), SYT2 (ENSG00000143858), SYTL5 (ENSG00000147041), SYT8 (ENSG00000149043), DOC2A (ENSG00000149927), SYTL3 (ENSG00000164674), TC2N (ENSG00000165929), SYT9 (ENSG00000170743), SYT12 (ENSG00000173227), RPH3AL (ENSG00000181031), C2CD4C (ENSG00000183186), C2CD4A (ENSG00000198535), SYT15 (ENSG00000204176), C2CD4B (ENSG00000205502), SYT3 (ENSG00000213023), DOC2B (ENSG00000272636), SYT15B (ENSG00000277758)

Protein

Protein identifiers

C2 calcium-dependent domain-containing protein 4D — B7Z1M9 (reviewed: B7Z1M9)

All UniProt accessions (1): B7Z1M9

RefSeq proteins (4): NP_001129475, NP_001381520, NP_001381521, NP_001381522 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000008	C2_dom	Domain
IPR035892	C2_domain_sf	Homologous_superfamily
IPR043549	C2C4C/C2C4D	Family

Pfam: PF00168

UniProt features (5 total): chain 1, domain 1, region of interest 1, compositionally biased region 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-B7Z1M9-F1	66.41	0.26

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 3 (showing top): chr1q21, DESCARTES_MAIN_FETAL_LYMPHATIC_ENDOTHELIAL_CELLS, HE_LIM_SUN_FETAL_LUNG_C1_SMG_CELL

GO Biological Process (0):

GO Molecular Function (0):

GO Cellular Component (0):

Protein interactions and networks

STRING

292 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
C2CD4D	SLC35G3	Q8N808	528
C2CD4D	OR2B11	Q5JQS5	505
C2CD4D	COL23A1	Q86Y22	480
C2CD4D	ZSCAN30	Q86W11	480
C2CD4D	GAB4	Q2WGN9	479
C2CD4D	DCAF4L2	Q8NA75	399
C2CD4D	THEM5	Q8N1Q8	396
C2CD4D	TMEM140	Q9NV12	369
C2CD4D	SH3YL1	Q96HL8	369
C2CD4D	AGAP3	Q96P47	366
C2CD4D	PAQR6	Q6TCH4	364
C2CD4D	ZSCAN26	Q16670	357
C2CD4D	CTU2	Q2VPK5	346
C2CD4D	RIMS2	Q9UQ26	343
C2CD4D	MTMR7	Q9Y216	330

IntAct

0 interactions, top by confidence:

BioGRID (3): C2CD4D (Affinity Capture-RNA), C2CD4D (Negative Genetic), CHD4 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A0A0U1RQ45, A0A0U1RQS6, A0A286YF58, A0A2R8YCJ5, A0A7I2V3R4, A2A699, A2VDX9, A6NCS6, A6NGB7, A6NJG2, A6NKF7, A6NKL6, A6NLJ0, A8MVW0, B2RU40, B7Z1M9, B8ZZ34, C9JH25, C9JVW0, D4A9R4, J3QNX5, M0QZC1, P03971, P0CG09, P0DPE3, Q0PHV7, Q0VD38, Q14761, Q29RK8, Q29RM6, Q2KJ18, Q2M3G4, Q2M3V2, Q5T442, Q64697, Q69YZ2, Q6F5E0, Q6NY19, Q6UXK2, Q80XF7

Diamond homologs: A6NLJ0, B7Z1M9, P0CG09, Q2KJ18, Q5HZI2, Q8NCU7, Q8TF44, Q17RD7

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	75
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
4796118	GRCh38/hg38 1q21.3(chr1:151707888-153275358)x1	Pathogenic

SpliceAI

351 predictions. Top by Δscore:

Variant	Effect	Δscore
1:151839221:C:CC	acceptor_gain	0.9700
1:151840455:T:TA	donor_gain	0.9700
1:151840202:CCT:C	donor_gain	0.9200
1:151839220:GC:G	acceptor_loss	0.9100
1:151839221:C:T	acceptor_loss	0.9100
1:151840197:TCCTA:T	donor_loss	0.9100
1:151840198:CCTAC:C	donor_loss	0.9100
1:151840199:CTACC:C	donor_loss	0.9100
1:151840200:TA:T	donor_loss	0.9100
1:151840201:ACCT:A	donor_loss	0.9100
1:151840202:C:CG	donor_loss	0.9100
1:151840203:C:A	donor_loss	0.9100
1:151839218:GGG:G	acceptor_gain	0.9000
1:151840196:GTCCT:G	donor_loss	0.9000
1:151840261:T:TA	donor_gain	0.9000
1:151839217:GGGG:G	acceptor_gain	0.8800
1:151839218:GGGCT:G	acceptor_gain	0.8800
1:151839219:GGCTG:G	acceptor_gain	0.8800
1:151839220:GCTGG:G	acceptor_gain	0.8800
1:151839860:T:A	donor_gain	0.8700
1:151839884:C:CT	donor_gain	0.8600
1:151839219:GG:G	acceptor_gain	0.8500
1:151839177:CCC:C	acceptor_gain	0.8400
1:151839178:CCC:C	acceptor_gain	0.8400
1:151839221:C:G	acceptor_gain	0.8400
1:151840204:T:A	donor_loss	0.8400
1:151839217:GGGGC:G	acceptor_gain	0.8200
1:151839222:T:A	acceptor_gain	0.8200
1:151839874:C:CA	donor_gain	0.8200
1:151840093:AGGC:A	donor_gain	0.8100

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000293983 (1:151837345 G>A), RS1000482938 (1:151842409 A>G), RS1002417879 (1:151840695 C>T), RS1002795354 (1:151841124 G>A,C), RS1003099428 (1:151839725 C>T), RS1003392308 (1:151839313 A>G), RS1003469859 (1:151838151 C>A), RS1004237064 (1:151840192 C>T), RS1005209498 (1:151842458 C>A), RS1005562165 (1:151839764 C>G,T), RS1006313455 (1:151841648 G>T), RS1006981953 (1:151838426 C>A,G,T), RS1007914001 (1:151840052 G>T), RS1008586158 (1:151837548 G>A), RS1008588917 (1:151838935 G>C,T)

Disease associations

OMIM: gene `` | disease phenotypes: MIM:616622

GenCC curated gene-disease

Mondo (1): autosomal recessive mendelian susceptibility to mycobacterial diseases due to complete RORgamma receptor deficiency (MONDO:0014710)

Orphanet (1): Mendelian susceptibility to mycobacterial diseases due to complete RORgamma receptor deficiency (Orphanet:477857)

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST008916_82	Asthma	5.000000e-27
GCST008916_88	Asthma	1.000000e-25

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

5 total (human), top 5 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
FR900359	decreases phosphorylation	1
triphenyl phosphate	affects expression	1
pentanal	decreases expression	1
Endosulfan	decreases expression	1

Clinical trials (associated diseases)

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