CBY2

Summary

CBY2 (chibby family member 2, HGNC:30720) is a protein-coding gene on chromosome 13q14.13, encoding Protein chibby homolog 2 (Q8NA61).

Enables identical protein binding activity. Predicted to be located in cytoplasmic vesicle.

Source: NCBI Gene 220082 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 89 total
• Dosage sensitivity (ClinGen): haploinsufficiency dosage sensitivity unlikely, triplosensitivity no evidence
• MANE Select transcript: NM_152719

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30720
Approved symbol	CBY2
Name	chibby family member 2
Location	13q14.13
Locus type	gene with protein product
Status	Approved
Aliases	NURIT
Ensembl gene	ENSG00000174015
Ensembl biotype	protein_coding
OMIM	618614
Entrez	220082

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000310521, ENST00000378966, ENST00000533564, ENST00000610924

RefSeq mRNA: 3 — MANE Select: NM_152719 NM_001286341, NM_001286342, NM_152719

CCDS: CCDS66540, CCDS9399

Canonical transcript exons

ENST00000310521 — 3 exons

Exon	Start	End
ENSE00001180319	45702775	45702855
ENSE00001913165	45713182	45714559
ENSE00002150255	45702320	45702465

Expression profiles

Bgee: expression breadth broad, 35 present calls, max score 94.49.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1834 / max 181.3362, expressed in 4 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
134979	0.0836	3
134982	0.0519	3
134981	0.0194	3
134980	0.0155	3
134978	0.0081	4
134983	0.0050	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	94.49	gold quality
right testis	UBERON:0004534	94.19	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	91.87	gold quality
testis	UBERON:0000473	90.81	gold quality
sperm	CL:0000019	90.22	gold quality
adult organism	UBERON:0007023	76.92	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	73.67	gold quality
skin of hip	UBERON:0001554	51.79	silver quality
placenta	UBERON:0001987	51.11	gold quality
buccal mucosa cell	CL:0002336	47.78	gold quality
upper leg skin	UBERON:0004262	44.56	silver quality
gingiva	UBERON:0001828	44.29	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	43.37	gold quality
Brodmann (1909) area 23	UBERON:0013554	43.29	gold quality
gingival epithelium	UBERON:0001949	43.00	gold quality
oocyte	CL:0000023	42.95	gold quality
quadriceps femoris	UBERON:0001377	42.90	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	42.86	gold quality
amniotic fluid	UBERON:0000173	42.85	gold quality
secondary oocyte	CL:0000655	42.57	gold quality
vastus lateralis	UBERON:0001379	42.57	gold quality
heart right ventricle	UBERON:0002080	42.33	gold quality
biceps brachii	UBERON:0001507	42.13	gold quality
cartilage tissue	UBERON:0002418	41.55	gold quality
superficial temporal artery	UBERON:0001614	41.33	gold quality
trabecular bone tissue	UBERON:0002483	41.24	gold quality
palpebral conjunctiva	UBERON:0001812	41.10	gold quality
mucosa of paranasal sinus	UBERON:0005030	40.98	gold quality
esophagus squamous epithelium	UBERON:0006920	40.93	gold quality
bone marrow cell	CL:0002092	40.64	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.13

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

9 targeting CBY2, 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-4682	100.00	68.89	1258
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-1228-3P	99.00	66.53	857
HSA-MIR-3921	97.81	67.45	1431
HSA-MIR-4653-5P	97.22	67.72	1429
HSA-MIR-4714-5P	97.04	67.76	955
HSA-MIR-6826-5P	93.80	67.42	514
HSA-MIR-4783-3P	73.56	61.87	82

Functional genomics

ClinGen dosage: haploinsufficiency 40 (dosage sensitivity unlikely), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Cby2	ENSMUSG00000034913
rattus_norvegicus	Cby2	ENSRNOG00000047413

Paralogs (3): CBY1 (ENSG00000100211), CCDC70 (ENSG00000123171), CBY3 (ENSG00000204659)

Protein

Protein identifiers

Protein chibby homolog 2 — Q8NA61 (reviewed: Q8NA61)

Alternative names: Spermatid-associated protein

All UniProt accessions (3): Q8NA61, A0A140VJV5, E9PLB4

UniProt curated annotations — full annotation on UniProt →

Subunit / interactions. Homodimer. Binds to NEK1.

Tissue specificity. Testis-specific.

Similarity. Belongs to the chibby family. SPERT subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8NA61-1	1	yes
Q8NA61-2	2

RefSeq proteins (3): NP_001273270, NP_001273271, NP_689932* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR028118	Chibby_fam	Family

Pfam: PF14645

UniProt features (22 total): modified residue 12, coiled-coil region 3, splice variant 2, compositionally biased region 2, chain 1, region of interest 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NA61-F1	63.75	0.25

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 (12): 97, 124, 144, 148, 150, 212, 225, 335, 338, 41, 86, 89

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 26 (showing top): E4F1_Q6, chr13q14, YKACATTT_UNKNOWN, BAKKER_FOXO3_TARGETS_DN, ZWANG_TRANSIENTLY_UP_BY_2ND_EGF_PULSE_ONLY, ZNF184_TARGET_GENES, MIR4682, MIR1228_3P, GSE17721_CTRL_VS_PAM3CSK4_2H_BMDC_DN, GSE17721_POLYIC_VS_PAM3CSK4_6H_BMDC_UP, GSE17721_LPS_VS_PAM3CSK4_2H_BMDC_DN, GSE17721_PAM3CSK4_VS_GADIQUIMOD_2H_BMDC_UP, GSE17721_LPS_VS_CPG_0.5H_BMDC_DN, GSE17721_POLYIC_VS_GARDIQUIMOD_12H_BMDC_UP, BDP1_TARGET_GENES

GO Biological Process (0):

GO Molecular Function (2): identical protein binding (GO:0042802), protein binding (GO:0005515)

GO Cellular Component (1): cytoplasmic vesicle (GO:0031410)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein binding	1
binding	1
cytoplasm	1
intracellular vesicle	1

Protein interactions and networks

STRING

1271 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CBY2	CBY3	A6NI87	708
CBY2	FAM187B	Q17R55	626
CBY2	KCTD4	Q8WVF5	605
CBY2	OR7G3	Q8NG95	602
CBY2	SPATA3	Q8NHX4	593
CBY2	SPEM1	Q8N4L4	582
CBY2	TMEM210	A6NLX4	559
CBY2	SPATC1	Q76KD6	549
CBY2	GTF2F2	P13984	537
CBY2	SMIM9	A6NGZ8	528
CBY2	SLC22A24	Q8N4F4	528
CBY2	C10orf120	Q5SQS8	520
CBY2	CBY1	Q9Y3M2	518
CBY2	SPATA45	Q537H7	517
CBY2	CYLC2	Q14093	512

IntAct

313 interactions, top by confidence:

A	B	Type	Score
CBY2	MLH1	psi-mi:“MI:0915”(physical association)	0.800
MLH1	CBY2	psi-mi:“MI:0915”(physical association)	0.800
CBY2	ZNF655	psi-mi:“MI:0915”(physical association)	0.670
CEP44	CBY2	psi-mi:“MI:0915”(physical association)	0.670
CBY2	METTL17	psi-mi:“MI:0915”(physical association)	0.670
CTNNAL1	CBY2	psi-mi:“MI:0915”(physical association)	0.670
CBY2	CEP44	psi-mi:“MI:0915”(physical association)	0.670
METTL17	CBY2	psi-mi:“MI:0915”(physical association)	0.670
CBY2	CTNNAL1	psi-mi:“MI:0915”(physical association)	0.670
ZNF655	CBY2	psi-mi:“MI:0915”(physical association)	0.670
TRIM42	CBY2	psi-mi:“MI:0915”(physical association)	0.560
	CBY2	psi-mi:“MI:0915”(physical association)	0.560
FRS3	CBY2	psi-mi:“MI:0915”(physical association)	0.560
EIF4E2	CBY2	psi-mi:“MI:0915”(physical association)	0.560
DUSP14	CBY2	psi-mi:“MI:0915”(physical association)	0.560
MOS	CBY2	psi-mi:“MI:0915”(physical association)	0.560
CBY2	ACTN1	psi-mi:“MI:0915”(physical association)	0.560
CBY2	LMO2	psi-mi:“MI:0915”(physical association)	0.560
CBY2	LMO1	psi-mi:“MI:0915”(physical association)	0.560
CBY2	RPL9	psi-mi:“MI:0915”(physical association)	0.560
TXLNA	CBY2	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (198): SPERT (Two-hybrid), SPERT (Two-hybrid), SPERT (Two-hybrid), SPERT (Two-hybrid), SPERT (Two-hybrid), SPERT (Two-hybrid), SPERT (Two-hybrid), SPERT (Two-hybrid), SPERT (Two-hybrid), SPERT (Two-hybrid), SPERT (Two-hybrid), SPERT (Two-hybrid), SPERT (Two-hybrid), SPERT (Two-hybrid), SPERT (Two-hybrid)

ESM2 similar proteins: A0A1B0GVQ3, A0A1W2PPK0, A0A1W2PPM1, A2A9I7, A6NCI8, A6QQS3, A7XCE8, E9PI22, E9PXT9, O15016, O91083, P09414, P0DMB1, P17923, P18804, P20879, P35965, P49750, Q0P670, Q12857, Q1RMX6, Q32LN6, Q32MG2, Q3B8N5, Q3T016, Q3V0A6, Q4JK59, Q5BI31, Q5T035, Q5ZKH6, Q642A3, Q6AXV6, Q6IMN6, Q6P1W5, Q6PEX7, Q6X4T0, Q80YD3, Q86UF4, Q8BII1, Q8C5V0

Diamond homologs: A1KXM5, Q6AXV6, Q8NA61, Q95JK3, A6NI87, A6QQS3, Q32MG2, Q9CVN6, Q8K4I6, Q8MJK1, Q9D1C2, Q9Y3M2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	84
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

370 predictions. Top by Δscore:

Variant	Effect	Δscore
13:45711451:GA:G	donor_gain	0.9900
13:45711499:GA:G	donor_gain	0.9900
13:45713180:AGAG:A	acceptor_gain	0.9900
13:45713180:AGAGG:A	acceptor_gain	0.9900
13:45713181:GAGG:G	acceptor_gain	0.9900
13:45713181:GAGGG:G	acceptor_gain	0.9900
13:45711469:TTTCA:T	donor_gain	0.9800
13:45713180:A:AG	acceptor_gain	0.9800
13:45713181:G:GG	acceptor_gain	0.9800
13:45713181:GA:G	acceptor_gain	0.9800
13:45713179:CAG:C	acceptor_gain	0.9700
13:45713180:AGA:A	acceptor_gain	0.9700
13:45713181:GAG:G	acceptor_gain	0.9700
13:45713176:CCGCA:C	acceptor_loss	0.9600
13:45713178:GCA:G	acceptor_loss	0.9600
13:45713181:G:T	acceptor_loss	0.9600
13:45711441:TCTCA:T	donor_gain	0.9400
13:45713169:T:G	acceptor_loss	0.9300
13:45713177:CGCAG:C	acceptor_gain	0.9300
13:45711523:GTCT:G	donor_gain	0.8800
13:45713149:GTTAA:G	acceptor_loss	0.8700
13:45713150:TTAA:T	acceptor_loss	0.8700
13:45713151:TAA:T	acceptor_loss	0.8700
13:45713177:C:A	acceptor_gain	0.8400
13:45711452:A:G	donor_gain	0.8200
13:45713325:A:AG	acceptor_gain	0.8100
13:45713326:G:GG	acceptor_gain	0.8100
13:45704264:G:GA	acceptor_gain	0.7900
13:45704475:G:GT	donor_gain	0.7900
13:45711549:T:G	donor_gain	0.7900

AlphaMissense

2935 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
13:45713413:T:C	F130L	0.996
13:45713415:C:A	F130L	0.996
13:45713415:C:G	F130L	0.996
13:45713428:T:A	W135R	0.996
13:45713428:T:C	W135R	0.996
13:45713430:G:C	W135C	0.996
13:45713430:G:T	W135C	0.996
13:45713414:T:C	F130S	0.992
13:45713429:G:C	W135S	0.988
13:45713407:T:C	F128L	0.987
13:45713409:C:A	F128L	0.987
13:45713409:C:G	F128L	0.987
13:45714254:A:C	Q410P	0.987
13:45714297:G:A	M424I	0.987
13:45714297:G:C	M424I	0.987
13:45714297:G:T	M424I	0.987
13:45713408:T:C	F128S	0.986
13:45714242:T:C	L406P	0.986
13:45713423:G:T	G133V	0.985
13:45714289:G:C	A422P	0.985
13:45714293:G:C	R423P	0.985
13:45714305:T:C	L427P	0.985
13:45714263:T:A	V413D	0.983
13:45713413:T:G	F130V	0.982
13:45713414:T:G	F130C	0.982
13:45713426:G:C	R134P	0.981
13:45713413:T:A	F130I	0.976
13:45714317:T:C	L431P	0.976
13:45714248:T:C	L408P	0.972
13:45713422:G:T	G133W	0.970

dbSNP variants (sampled 300 via entrez): RS1000054342 (13:45711504 G>T), RS1000390462 (13:45700602 A>G), RS1000587166 (13:45714154 C>T), RS1000760744 (13:45700390 C>T), RS1000847529 (13:45700921 A>G), RS1001242939 (13:45711367 A>C), RS1001495833 (13:45712755 G>A,C), RS1001771387 (13:45704861 G>C), RS1002133261 (13:45706205 G>C), RS1002418985 (13:45706564 C>A,G), RS1002506803 (13:45706432 G>C), RS1002802546 (13:45702852 T>G), RS1002821396 (13:45713577 G>A,T), RS1003437072 (13:45708220 A>G), RS1003609076 (13:45709736 G>C,T)

Disease associations

OMIM: gene MIM:618614 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

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

6 total (human), top 6 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
ferrous chloride	decreases expression	1
CGP 52608	affects binding, increases reaction	1
Arsenic	affects methylation	1
Estradiol	decreases expression	1
Silicon Dioxide	decreases expression	1
Tobacco Smoke Pollution	affects expression	1

Clinical trials (associated diseases)

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