CRYBG3

Summary

CRYBG3 (crystallin beta-gamma domain containing 3, HGNC:34427) is a protein-coding gene on chromosome 3q11.2, encoding Very large A-kinase anchor protein (Q68DQ2). Anchoring protein that mediates the subcellular compartmentation of protein kinase A (PKA).

Enables protein kinase A binding activity. Predicted to be involved in lens development in camera-type eye and visual perception. Part of protein-containing complex.

Source: NCBI Gene 131544 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 35 total
• MANE Select transcript: NM_153605

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:34427
Approved symbol	CRYBG3
Name	crystallin beta-gamma domain containing 3
Location	3q11.2
Locus type	gene with protein product
Status	Approved
Aliases	DKFZp667G2110
Ensembl gene	ENSG00000080200
Ensembl biotype	protein_coding
OMIM	620146
Entrez	131544

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000389622, ENST00000485253, ENST00000495403

RefSeq mRNA: 1 — MANE Select: NM_153605 NM_153605

CCDS: CCDS43113

Canonical transcript exons

ENST00000389622 — 22 exons

Exon	Start	End
ENSE00001156371	97915610	97915736
ENSE00001156624	97912167	97912276
ENSE00001240224	97900453	97900485
ENSE00001240230	97899137	97899263
ENSE00001240236	97898883	97899025
ENSE00001240244	97895959	97896085
ENSE00001240252	97892860	97892993
ENSE00001240266	97889355	97889390
ENSE00001405465	97881072	97881219
ENSE00001419690	97888341	97888455
ENSE00001434556	97886631	97886767
ENSE00001506388	97879985	97880100
ENSE00001506389	97879704	97879748
ENSE00001852506	97943226	97944984
ENSE00003476229	97936785	97936908
ENSE00003496686	97933694	97933833
ENSE00003510385	97942284	97942443
ENSE00003662334	97941148	97941306
ENSE00003712721	97822011	97822355
ENSE00003730826	97864217	97864647
ENSE00003741670	97843195	97843261
ENSE00003745340	97871842	97878037

Expression profiles

Bgee: expression breadth ubiquitous, 287 present calls, max score 95.52.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 16.8987 / max 271.3708, expressed in 1709 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
37516	9.5470	1626
37515	7.1310	1571
37521	0.2206	70

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
gingival epithelium	UBERON:0001949	95.52	gold quality
pericardium	UBERON:0002407	94.79	gold quality
gingiva	UBERON:0001828	94.67	gold quality
germinal epithelium of ovary	UBERON:0001304	93.14	gold quality
inferior olivary complex	UBERON:0002127	92.66	gold quality
colonic epithelium	UBERON:0000397	92.64	gold quality
upper leg skin	UBERON:0004262	92.53	gold quality
parietal pleura	UBERON:0002400	92.46	gold quality
skin of hip	UBERON:0001554	92.39	gold quality
cardia of stomach	UBERON:0001162	92.27	gold quality
oviduct epithelium	UBERON:0004804	92.22	gold quality
tongue squamous epithelium	UBERON:0006919	92.04	gold quality
pleura	UBERON:0000977	92.02	gold quality
mammalian vulva	UBERON:0000997	91.93	gold quality
epithelium of nasopharynx	UBERON:0001951	91.77	gold quality
visceral pleura	UBERON:0002401	91.71	gold quality
lower lobe of lung	UBERON:0008949	91.57	gold quality
squamous epithelium	UBERON:0006914	91.25	gold quality
corpus callosum	UBERON:0002336	91.15	gold quality
sperm	CL:0000019	91.13	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	91.09	gold quality
cervix epithelium	UBERON:0004801	91.07	gold quality
cervix squamous epithelium	UBERON:0006922	90.79	silver quality
mammary duct	UBERON:0001765	90.62	gold quality
choroid plexus epithelium	UBERON:0003911	90.62	gold quality
heart right ventricle	UBERON:0002080	90.39	gold quality
trigeminal ganglion	UBERON:0001675	90.31	gold quality
epithelium of mammary gland	UBERON:0003244	90.25	gold quality
calcaneal tendon	UBERON:0003701	90.24	gold quality
male germ cell	CL:0000015	90.12	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-11121	yes	684.04
E-ANND-3	yes	7.87

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

110 targeting CRYBG3, 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-3163	100.00	77.23	8605
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-10523-5P	99.91	69.22	2038
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-20B-5P	99.88	74.01	2621
HSA-MIR-519D-3P	99.88	73.97	2607
HSA-MIR-526B-3P	99.88	74.06	2587
HSA-MIR-93-5P	99.88	73.98	2606
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-6857-5P	99.87	65.32	985
HSA-MIR-8067	99.86	69.59	2260

Literature-anchored findings (GeneRIF, showing 2)

• Long Non-Coding RNA CRYBG3 Promotes Lung Cancer Metastasis via Activating the eEF1A1/MDM2/MTBP Axis. (PMID:33809929)
• Ionizing radiation-induced long noncoding RNA CRYBG3 regulates YAP/TAZ through mechanotransduction. (PMID:35246511)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Crybg3	ENSMUSG00000022723
rattus_norvegicus	Crybg3	ENSRNOG00000045728

Paralogs (14): CRYBB3 (ENSG00000100053), CRYBB1 (ENSG00000100122), CRYBA1 (ENSG00000108255), CRYBG1 (ENSG00000112297), CRYGD (ENSG00000118231), CRYGN (ENSG00000127377), CRYGC (ENSG00000163254), CRYBA2 (ENSG00000163499), CRYGA (ENSG00000168582), CRYBG2 (ENSG00000176092), CRYGB (ENSG00000182187), CRYBA4 (ENSG00000196431), CRYGS (ENSG00000213139), CRYBB2 (ENSG00000244752)

Protein

Protein identifiers

Very large A-kinase anchor protein — Q68DQ2 (reviewed: Q68DQ2)

Alternative names: Beta/gamma crystallin domain-containing protein 3

All UniProt accessions (2): Q68DQ2, C9J659

UniProt curated annotations — full annotation on UniProt →

Function. Anchoring protein that mediates the subcellular compartmentation of protein kinase A (PKA).

Subunit / interactions. Isoform vlAKAP binds to dimeric RII-alpha regulatory subunit of PKA (PRKAR2A/PRKAR2B).

Similarity. Belongs to the beta/gamma-crystallin family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q68DQ2-3	vlAKAP	yes
Q68DQ2-1	1
Q68DQ2-2	2

RefSeq proteins (1): NP_705833* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000772	Ricin_B_lectin	Domain
IPR001064	Beta/gamma_crystallin	Domain
IPR011024	G_crystallin-like	Homologous_superfamily
IPR035992	Ricin_B-like_lectins	Homologous_superfamily
IPR050252	Beta/Gamma-Crystallin	Family

Pfam: PF00030, PF00652

UniProt features (47 total): domain 10, region of interest 10, compositionally biased region 10, modified residue 6, sequence conflict 4, splice variant 3, sequence variant 3, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

No AlphaFold model available for Q68DQ2 — AlphaFold DB does not currently provide models for proteins above ~3000 aa.

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 (6): 931, 2086, 2093, 2094, 2100, 2104

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 152 (showing top): WAMUNYOKOLI_OVARIAN_CANCER_LMP_DN, GCM_ZNF198, ASTON_MAJOR_DEPRESSIVE_DISORDER_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_SENSORY_PERCEPTION_OF_LIGHT_STIMULUS, KINSEY_TARGETS_OF_EWSR1_FLII_FUSION_DN, GOBP_SENSORY_PERCEPTION, GOBP_SENSORY_ORGAN_DEVELOPMENT, LOPEZ_MESOTHELIOMA_SURVIVAL_UP, GOBP_LENS_DEVELOPMENT_IN_CAMERA_TYPE_EYE, DURCHDEWALD_SKIN_CARCINOGENESIS_DN, MASSARWEH_TAMOXIFEN_RESISTANCE_UP, GOMF_PROTEIN_KINASE_A_BINDING, GOMF_STRUCTURAL_CONSTITUENT_OF_EYE_LENS, GOMF_STRUCTURAL_MOLECULE_ACTIVITY

GO Biological Process (2): lens development in camera-type eye (GO:0002088), visual perception (GO:0007601)

GO Molecular Function (3): structural constituent of eye lens (GO:0005212), carbohydrate binding (GO:0030246), protein kinase A binding (GO:0051018)

GO Cellular Component (1): protein-containing complex (GO:0032991)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
camera-type eye development	1
anatomical structure development	1
sensory perception of light stimulus	1
structural molecule activity	1
binding	1
protein binding	1
cellular_component	1

Protein interactions and networks

STRING

376 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CRYBG3	CUEDC2	Q9H467	575
CRYBG3	LDHA	P00338	561
CRYBG3	CRYZL1	O95825	488
CRYBG3	PTTG2	Q9NZH5	434
CRYBG3	PTTG1	O95997	410
CRYBG3	DAB2IP	Q5VWQ8	394
CRYBG3	LGSN	Q5TDP6	373
CRYBG3	CRYL1	Q9Y2S2	371
CRYBG3	ZNF772	Q68DY9	366
CRYBG3	IFFO2	Q5TF58	338
CRYBG3	CRYZ	Q08257	324
CRYBG3	POM121L12	Q8N7R1	303
CRYBG3	PPA1	Q15181	302
CRYBG3	UBE2C	O00762	301
CRYBG3	PCDHGB3	Q9Y5G1	299

IntAct

50 interactions, top by confidence:

A	B	Type	Score
GSK3A	AXIN1	psi-mi:“MI:0914”(association)	0.800
MLF1	DNAJB6	psi-mi:“MI:0914”(association)	0.750
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
MOS	HSP90AA1	psi-mi:“MI:0914”(association)	0.560
NPAS1	DNAJB5	psi-mi:“MI:0914”(association)	0.530
MLF1	NDC80	psi-mi:“MI:0914”(association)	0.530
TSSK1B	HSPA8	psi-mi:“MI:0914”(association)	0.530
CTSG	MANBA	psi-mi:“MI:0914”(association)	0.530
ZMYND11	CRYBG3	psi-mi:“MI:0407”(direct interaction)	0.440
GSK3B	SEC16A	psi-mi:“MI:2364”(proximity)	0.420
Prkar2a	TBC1D31	psi-mi:“MI:0914”(association)	0.350
	PGRMC1	psi-mi:“MI:0914”(association)	0.350
BVLF1	VWA8	psi-mi:“MI:0914”(association)	0.350
PRKAR2B	PALM2AKAP2	psi-mi:“MI:0914”(association)	0.350
NTRK1	ILVBL	psi-mi:“MI:0914”(association)	0.350
HSPA4	HSPA8	psi-mi:“MI:0914”(association)	0.350
IPO5	C11orf98	psi-mi:“MI:0914”(association)	0.350
PRKACA	ZNF724	psi-mi:“MI:0914”(association)	0.350
S100A2	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
PRKAR1B	DNAJC13	psi-mi:“MI:0914”(association)	0.350
DUOXA2	CHRNB1	psi-mi:“MI:0914”(association)	0.350
KCNAB2	LONP1	psi-mi:“MI:0914”(association)	0.350
KLK2	VWA8	psi-mi:“MI:0914”(association)	0.350
PRKAR2B	AKAP10	psi-mi:“MI:0914”(association)	0.350
RPL28	LEFTY2	psi-mi:“MI:0914”(association)	0.350
SLC25A25	MCM3AP	psi-mi:“MI:0914”(association)	0.350
UPK2	IFT56	psi-mi:“MI:0914”(association)	0.350

BioGRID (93): CRYBG3 (Affinity Capture-MS), CRYBG3 (Affinity Capture-MS), CRYBG3 (Affinity Capture-MS), CRYBG3 (Proximity Label-MS), CRYBG3 (Proximity Label-MS), CRYBG3 (Affinity Capture-MS), CRYBG3 (Proximity Label-MS), CRYBG3 (Affinity Capture-MS), CRYBG3 (Affinity Capture-MS), CRYBG3 (Affinity Capture-MS), CRYBG3 (Affinity Capture-MS), CRYBG3 (Proximity Label-MS), CRYBG3 (Proximity Label-MS), CRYBG3 (Proximity Label-MS), CRYBG3 (Proximity Label-MS)

ESM2 similar proteins: A0A140LI88, A4D1E1, D3Z987, D3ZUC6, E5FYH0, E5FYH1, E9Q3S4, F6ULY3, F7DF15, G3S077, G7H7V7, G7NY55, O35923, O54952, O88491, O95405, P38398, P48754, P51587, P97929, Q0VBV7, Q0VGT4, Q2M3C7, Q3V089, Q56UN5, Q5DTT3, Q5F2C3, Q5VWN6, Q61493, Q68DQ2, Q6J6I8, Q6J6I9, Q6J6J0, Q6NSW3, Q6ZP01, Q7TSY8, Q7Z570, Q80U44, Q864S8, Q864U1

Diamond homologs: A2IBH5, A2IBY7, A2ICR5, A3RLD7, A3RLD8, A3RLE1, A3RLE2, A4L9I8, A4L9I9, A4QNB6, D3ZEG1, F6Q2R9, O35486, P02522, P02523, P02524, P02525, P02526, P02527, P02528, P02529, P02530, P02531, P04342, P04344, P04345, P05813, P06504, P07315, P07316, P07317, P07318, P07320, P07530, P08209, P0C5E9, P10042, P10043, P10065, P10066

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	3
Likely benign	8
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

3146 predictions. Top by Δscore:

Variant	Effect	Δscore
3:97864214:A:G	acceptor_gain	1.0000
3:97864643:CTAAA:C	donor_gain	1.0000
3:97864648:G:GG	donor_gain	1.0000
3:97879702:A:AG	acceptor_gain	1.0000
3:97879703:G:GG	acceptor_gain	1.0000
3:97879703:GA:G	acceptor_gain	1.0000
3:97879746:AAG:A	donor_loss	1.0000
3:97879749:G:T	donor_loss	1.0000
3:97879750:T:A	donor_loss	1.0000
3:97879978:GTTGC:G	acceptor_loss	1.0000
3:97879979:TTGCA:T	acceptor_loss	1.0000
3:97879980:TGCAG:T	acceptor_loss	1.0000
3:97879981:GCAG:G	acceptor_loss	1.0000
3:97879982:CAG:C	acceptor_loss	1.0000
3:97879983:A:AG	acceptor_gain	1.0000
3:97879983:AG:A	acceptor_loss	1.0000
3:97879983:AGAT:A	acceptor_gain	1.0000
3:97879984:G:GG	acceptor_gain	1.0000
3:97879984:GAT:G	acceptor_gain	1.0000
3:97879984:GATG:G	acceptor_gain	1.0000
3:97880087:GTT:G	donor_gain	1.0000
3:97880096:GGCTG:G	donor_gain	1.0000
3:97880097:GCTG:G	donor_gain	1.0000
3:97880097:GCTGG:G	donor_gain	1.0000
3:97880098:CTG:C	donor_loss	1.0000
3:97880099:TGG:T	donor_loss	1.0000
3:97880100:GG:G	donor_loss	1.0000
3:97880101:G:GG	donor_gain	1.0000
3:97880101:GTA:G	donor_loss	1.0000
3:97880102:T:G	donor_loss	1.0000

AlphaMissense

19743 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:97936786:T:A	W2795R	0.999
3:97936786:T:C	W2795R	0.999
3:97936855:T:A	W2818R	0.999
3:97936855:T:C	W2818R	0.999
3:97943294:T:A	W2965R	0.999
3:97943294:T:C	W2965R	0.999
3:97881073:T:A	W2336R	0.998
3:97881073:T:C	W2336R	0.998
3:97888342:T:A	W2431R	0.998
3:97888342:T:C	W2431R	0.998
3:97895960:T:A	W2526R	0.998
3:97895960:T:C	W2526R	0.998
3:97899013:T:A	V2611D	0.998
3:97899138:T:A	W2616R	0.998
3:97899138:T:C	W2616R	0.998
3:97933721:T:C	F2757L	0.998
3:97933723:T:A	F2757L	0.998
3:97933723:T:G	F2757L	0.998
3:97933811:T:C	S2787P	0.998
3:97936857:G:C	W2818C	0.998
3:97936857:G:T	W2818C	0.998
3:97936895:G:C	R2831P	0.998
3:97942377:T:A	W2920R	0.998
3:97942377:T:C	W2920R	0.998
3:97899216:T:A	W2642R	0.997
3:97899216:T:C	W2642R	0.997
3:97933719:T:C	L2756P	0.997
3:97933742:G:A	G2764R	0.997
3:97933742:G:C	G2764R	0.997
3:97936888:T:C	S2829P	0.997

dbSNP variants (sampled 300 via entrez): RS1000069027 (3:97944780 A>T), RS1000086957 (3:97842988 A>G), RS1000128156 (3:97937374 C>A), RS1000136898 (3:97890407 A>G), RS1000148450 (3:97918910 G>A,T), RS1000194826 (3:97883131 C>G), RS1000195937 (3:97826763 A>G), RS1000197163 (3:97836719 A>G), RS1000222715 (3:97830099 A>G,T), RS1000233342 (3:97935156 C>A), RS1000245044 (3:97848537 G>A), RS1000248397 (3:97849833 G>T), RS1000253645 (3:97829733 G>A), RS1000284676 (3:97830085 A>G), RS1000287286 (3:97929819 AT>A,ATT)

Disease associations

OMIM: gene MIM:620146 | 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

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression	3
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
triphenyl phosphate	affects expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
butyraldehyde	decreases expression	1
nickel sulfate	decreases expression	1
coumarin	affects phosphorylation	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
entinostat	decreases expression	1
abrine	decreases expression	1
Resveratrol	increases expression, affects cotreatment	1
Acetaminophen	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Cadmium	increases abundance, increases expression	1
Caffeine	affects phosphorylation	1
Calcitriol	increases expression	1
Folic Acid	decreases expression	1
Methyl Methanesulfonate	decreases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Tretinoin	increases expression	1
Urethane	increases expression	1
Cadmium Chloride	increases abundance, increases expression	1
Okadaic Acid	increases expression	1
Copper Sulfate	decreases expression	1
Lactic Acid	decreases expression	1
Particulate Matter	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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