CC2D2B

Summary

CC2D2B (coiled-coil and C2 domain containing 2B, HGNC:31666) is a protein-coding gene on chromosome 10q24.1, encoding Protein CC2D2B (Q6DHV5).

Predicted to be involved in non-motile cilium assembly and protein localization to ciliary transition zone. Predicted to be active in ciliary transition zone.

Source: NCBI Gene 387707 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 61 total
• MANE Select transcript: NM_001349008

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:31666
Approved symbol	CC2D2B
Name	coiled-coil and C2 domain containing 2B
Location	10q24.1
Locus type	gene with protein product
Status	Approved
Aliases	bA248J23.4, bA690P14.3
Ensembl gene	ENSG00000188649
Ensembl biotype	protein_coding
Entrez	387707

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 4 protein_coding, 3 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay, 1 retained_intron

ENST00000344386, ENST00000410012, ENST00000423344, ENST00000424464, ENST00000472454, ENST00000475252, ENST00000484685, ENST00000602648, ENST00000636965, ENST00000646931

RefSeq mRNA: 4 — MANE Select: NM_001349008 NM_001001732, NM_001130446, NM_001159747, NM_001349008

CCDS: CCDS58090, CCDS91310

Canonical transcript exons

ENST00000646931 — 35 exons

Exon	Start	End
ENSE00001197550	95927237	95927332
ENSE00001454588	96019702	96019824
ENSE00001454589	96019203	96019337
ENSE00001454590	96016201	96016314
ENSE00001454591	96013788	96013877
ENSE00001454592	96012532	96012729
ENSE00001578246	96024853	96024911
ENSE00001664961	96012185	96012367
ENSE00003543403	95922016	95922076
ENSE00003548504	95924314	95924390
ENSE00003559012	95981975	95982113
ENSE00003572538	96009825	96009923
ENSE00003609683	95924779	95924844
ENSE00003636128	96027212	96027389
ENSE00003642895	95983606	95983809
ENSE00003777929	95992527	95992697
ENSE00003791916	95937991	95938189
ENSE00003793023	95961829	95961969
ENSE00003793228	95938797	95938925
ENSE00003794801	95955394	95955491
ENSE00003795476	95965896	95965998
ENSE00003796403	95949896	95950105
ENSE00003797278	96004152	96004248
ENSE00003797660	95966190	95966302
ENSE00003798704	95991370	95991461
ENSE00003800626	95938569	95938705
ENSE00003815172	95995269	95995365
ENSE00003816002	95988250	95988342
ENSE00003817661	95972066	95972216
ENSE00003822753	95996143	95996252
ENSE00003827009	95968724	95968901
ENSE00003827401	95974009	95974156
ENSE00003842365	95911301	95911359
ENSE00003899825	96031820	96033745
ENSE00003900795	95907975	95908057

Expression profiles

Bgee: expression breadth ubiquitous, 165 present calls, max score 93.12.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
kidney epithelium	UBERON:0004819	93.12	gold quality
cardiac muscle of right atrium	UBERON:0003379	91.66	gold quality
left ventricle myocardium	UBERON:0006566	91.63	gold quality
superficial temporal artery	UBERON:0001614	87.30	silver quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.85	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.18	gold quality
mucosa of paranasal sinus	UBERON:0005030	84.18	gold quality
epithelial cell of pancreas	CL:0000083	83.57	gold quality
sperm	CL:0000019	81.43	silver quality
epithelium of nasopharynx	UBERON:0001951	80.98	gold quality
upper arm skin	UBERON:0004263	80.43	gold quality
germinal epithelium of ovary	UBERON:0001304	80.02	gold quality
myocardium	UBERON:0002349	79.30	gold quality
cardia of stomach	UBERON:0001162	77.05	gold quality
gingival epithelium	UBERON:0001949	75.36	gold quality
nasal cavity epithelium	UBERON:0005384	74.44	gold quality
tibial artery	UBERON:0007610	72.56	gold quality
popliteal artery	UBERON:0002250	72.55	gold quality
vastus lateralis	UBERON:0001379	72.33	gold quality
quadriceps femoris	UBERON:0001377	71.89	gold quality
corpus callosum	UBERON:0002336	71.46	gold quality
saphenous vein	UBERON:0007318	71.43	gold quality
colonic epithelium	UBERON:0000397	71.11	gold quality
epithelium of mammary gland	UBERON:0003244	71.11	gold quality
mammary duct	UBERON:0001765	70.92	gold quality
gingiva	UBERON:0001828	70.84	gold quality
mucosa of stomach	UBERON:0001199	70.82	gold quality
secondary oocyte	CL:0000655	70.47	gold quality
right coronary artery	UBERON:0001625	70.17	gold quality
calcaneal tendon	UBERON:0003701	70.08	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	6.39

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 1)

• The CC2D2B is a novel genetic modifier of the clinical phenotype in patients with hereditary angioedema due to C1 inhibitor deficiency. (PMID:38679185)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Cc2d2b	ENSMUSG00000108929
rattus_norvegicus	Cc2d2b	ENSRNOG00000070964
drosophila_melanogaster	Cc2d2a	FBGN0263113
caenorhabditis_elegans	mks-6	WBGENE00010642

Paralogs (2): CC2D2A (ENSG00000048342), CEP76 (ENSG00000101624)

Protein

Protein identifiers

Protein CC2D2B — Q6DHV5 (reviewed: Q6DHV5)

All UniProt accessions (5): A0A1B0GUL2, A0A1W2PQR2, A0A5S8K7B6, Q6DHV5, R4GN90

Isoforms (4)

UniProt ID	Names	Canonical?
Q6DHV5-5	1	yes
Q6DHV5-1	2
Q6DHV5-2	3
Q6DHV5-4	4

RefSeq proteins (2): NP_001123918, NP_001335937* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000008	C2_dom	Domain
IPR028928	CC2D2AN-C2	Domain
IPR035892	C2_domain_sf	Homologous_superfamily
IPR041510	DUF5523	Domain
IPR052434	Tectonic-like_complex_comp	Family
IPR056288	CEP76_C	Domain
IPR056290	CEPT76/DRC7_peptidase-like_dom	Domain

Pfam: PF15625, PF17661, PF24652, PF24656

UniProt features (11 total): splice variant 6, sequence variant 3, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6DHV5-F1	68.49	0.14

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 66 (showing top): AAGCAAT_MIR137, GOBP_PROTEIN_LOCALIZATION_TO_CILIUM, GOBP_CILIUM_ORGANIZATION, GOBP_ORGANELLE_ASSEMBLY, ATGCTGG_MIR338, LYF1_01, TCCAGAT_MIR5165P, GOBP_PROTEIN_LOCALIZATION_TO_ORGANELLE, GOBP_CELL_PROJECTION_ORGANIZATION, ACEVEDO_METHYLATED_IN_LIVER_CANCER_DN, GOCC_CILIARY_TRANSITION_ZONE, WGTTNNNNNAAA_UNKNOWN, GOCC_CILIUM, ATACTGT_MIR144, GOBP_PROTEIN_LOCALIZATION_TO_CILIARY_TRANSITION_ZONE

GO Biological Process (2): protein localization to ciliary transition zone (GO:1904491), non-motile cilium assembly (GO:1905515)

GO Molecular Function (0):

GO Cellular Component (1): ciliary transition zone (GO:0035869)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein localization to cilium	1
cilium assembly	1
cilium	1
cellular anatomical structure	1

Protein interactions and networks

STRING

340 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CC2D2B	C3orf22	Q8N5N4	591
CC2D2B	RNASE12	Q5GAN4	570
CC2D2B	C12orf56	Q8IXR9	544
CC2D2B	SMIM17	P0DL12	541
CC2D2B	ANKRD62	A6NC57	509
CC2D2B	SH2D7	A6NKC9	508
CC2D2B	C22orf42	Q6IC83	507
CC2D2B	C1orf167	Q5SNV9	507
CC2D2B	SPDYE4	A6NLX3	505
CC2D2B	CLPSL1	A2RUU4	479
CC2D2B	EPCIP	Q9NYP8	479
CC2D2B	RD3L	P0DJH9	478
CC2D2B	SMIM21	Q3B7S5	476
CC2D2B	SPATA12	Q7Z6I5	447
CC2D2B	MGAT4D	A6NG13	447

IntAct

2 interactions, top by confidence:

A	B	Type	Score
RALGDS	CC2D2B	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (6): CC2D2B (Proximity Label-MS), CC2D2B (Affinity Capture-MS), CC2D2B (Affinity Capture-MS), ACSBG1 (Cross-Linking-MS (XL-MS)), EIF5A2 (Cross-Linking-MS (XL-MS)), CHMP6 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A2RRS8, A4D1B5, A5PLK6, D3Z6S9, E7FA21, G3UYX5, O75747, O75901, O88480, O88869, Q2T9P0, Q3UMB5, Q3UPC7, Q3URV1, Q402B2, Q4R9E9, Q5SUS0, Q5T0N1, Q5XI56, Q5XX13, Q642P2, Q6DHV5, Q6INI0, Q6P2C0, Q7L0X2, Q80X60, Q86VV8, Q86WZ0, Q8CDN1, Q8IV33, Q8IXR9, Q8K342, Q8N7B9, Q8N7X0, Q8ND61, Q8NE09, Q8NG48, Q8R4Y8, Q8TDY2, Q8TEV9

Diamond homologs: Q6DHV5, Q8CFW7, Q95K30, Q9P2K1

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	45
Likely benign	6
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3309 predictions. Top by Δscore:

Variant	Effect	Δscore
10:95911300:GAAA:G	acceptor_gain	1.0000
10:95922084:A:AG	donor_gain	1.0000
10:95922088:G:GG	donor_gain	1.0000
10:95924386:CTAAG:C	donor_loss	1.0000
10:95924387:TAAG:T	donor_loss	1.0000
10:95924388:AAGGT:A	donor_loss	1.0000
10:95924389:AG:A	donor_loss	1.0000
10:95924390:GGTAA:G	donor_loss	1.0000
10:95924391:GTAAT:G	donor_loss	1.0000
10:95924392:T:A	donor_loss	1.0000
10:95924774:TTCA:T	acceptor_loss	1.0000
10:95924775:TCAG:T	acceptor_loss	1.0000
10:95924776:CAG:C	acceptor_loss	1.0000
10:95924777:A:AG	acceptor_gain	1.0000
10:95924777:A:C	acceptor_loss	1.0000
10:95924778:G:GA	acceptor_gain	1.0000
10:95924778:GATT:G	acceptor_gain	1.0000
10:95924778:GATTA:G	acceptor_gain	1.0000
10:95924839:TCCA:T	donor_gain	1.0000
10:95924840:CCAAG:C	donor_loss	1.0000
10:95924842:AAGG:A	donor_loss	1.0000
10:95924843:AGGT:A	donor_loss	1.0000
10:95924845:G:A	donor_loss	1.0000
10:95924846:T:A	donor_loss	1.0000
10:95938565:AAAGT:A	acceptor_gain	1.0000
10:96009821:ATAG:A	acceptor_gain	1.0000
10:96019820:TACAG:T	donor_loss	1.0000
10:96019821:ACAG:A	donor_loss	1.0000
10:96019822:CAG:C	donor_loss	1.0000
10:96019823:AG:A	donor_loss	1.0000

AlphaMissense

9590 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:95949969:T:C	L292P	0.996
10:95996224:T:A	W941R	0.996
10:95996224:T:C	W941R	0.996
10:95974089:T:A	W626R	0.995
10:95974089:T:C	W626R	0.995
10:95938686:G:C	R218P	0.994
10:95949990:T:C	F299S	0.994
10:96027226:T:C	L1321P	0.994
10:95972169:T:C	F583S	0.992
10:96019771:T:A	W1279R	0.992
10:96019771:T:C	W1279R	0.992
10:95950038:T:C	L315P	0.991
10:96027250:G:C	R1329P	0.991
10:96031931:G:C	A1413P	0.991
10:95972168:T:C	F583L	0.990
10:95972170:T:A	F583L	0.990
10:95972170:T:G	F583L	0.990
10:95983718:T:C	L732P	0.990
10:95996226:G:C	W941C	0.989
10:95996226:G:T	W941C	0.989
10:95974072:T:C	L620P	0.988
10:95983708:C:A	R729S	0.988
10:95968798:T:A	V514D	0.987
10:95992660:G:C	A869P	0.987
10:95996168:T:A	V922D	0.987
10:95968739:A:C	R494S	0.986
10:95968739:A:T	R494S	0.986
10:95968777:T:A	I507K	0.986
10:95972213:A:C	S598R	0.986
10:95972215:C:A	S598R	0.986

dbSNP variants (sampled 300 via entrez): RS1000011125 (10:95932227 G>T), RS1000035530 (10:95914694 C>G), RS1000055699 (10:95974955 T>A), RS1000055967 (10:96026641 C>T), RS1000066435 (10:95922954 A>T), RS1000142164 (10:95956616 C>T), RS1000207715 (10:95982760 G>A), RS1000223528 (10:95929360 G>A), RS1000254780 (10:95926316 T>C), RS1000257252 (10:96020980 A>G,T), RS1000279959 (10:95982403 T>C), RS1000314031 (10:95915448 A>G), RS1000374172 (10:96018786 T>G), RS1000393930 (10:95984146 C>T), RS1000467743 (10:95911146 T>C,G)

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

3 associations (top):

Study	Trait	p-value
GCST006479_24	Diverticular disease	9.000000e-06
GCST009174_2	Response to (pegylated) interferon in chronic hepatitis B	1.000000e-06
GCST010726_42	Periventricular white matter hyperintensities	5.000000e-07

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0009959	diverticular disease
EFO:0007859	response to interferon
EFO:0005665	white matter hyperintensity measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

15 total (human), top 15 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
triphenyl phosphate	affects expression	1
propionaldehyde	decreases expression	1
beta-lapachone	decreases expression	1
4-aminophenylarsenoxide	affects binding, decreases reaction	1
di-n-butylphosphoric acid	affects expression	1
theaflavin-3,3’-digallate	affects expression	1
Arsenic Trioxide	affects binding, decreases reaction	1
Benzo(a)pyrene	increases methylation	1
Cadmium	increases abundance, increases expression	1
Mercuric Chloride	decreases expression	1
Dronabinol	increases expression	1
Thimerosal	decreases expression	1
Tretinoin	increases expression	1
Antirheumatic Agents	decreases expression	1
Cadmium Chloride	increases abundance, increases expression	1

Clinical trials (associated diseases)

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