CRYBG1

Summary

CRYBG1 (crystallin beta-gamma domain containing 1, HGNC:356) is a protein-coding gene on chromosome 6q21, encoding Beta/gamma crystallin domain-containing protein 1 (Q9Y4K1). May function as suppressor of malignant melanoma.

Predicted to enable carbohydrate binding activity.

Source: NCBI Gene 202 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 316 total
• Druggable target: yes
• MANE Select transcript: NM_001371242

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:356
Approved symbol	CRYBG1
Name	crystallin beta-gamma domain containing 1
Location	6q21
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000112297
Ensembl biotype	protein_coding
OMIM	601797
Entrez	202

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 3 protein_coding, 1 retained_intron

ENST00000457437, ENST00000487681, ENST00000633556, ENST00000651520

RefSeq mRNA: 2 — MANE Select: NM_001371242 NM_001371242, NM_001624

CCDS: CCDS93984

Canonical transcript exons

ENST00000633556 — 22 exons

Exon	Start	End
ENSE00002435584	106544571	106544697
ENSE00002435881	106525133	106525180
ENSE00002442110	106543440	106543597
ENSE00002453244	106525268	106525386
ENSE00002460153	106552184	106552216
ENSE00002470571	106561342	106561500
ENSE00002475307	106551852	106551978
ENSE00002477682	106539403	106539529
ENSE00002483406	106563764	106563926
ENSE00002486887	106560803	106560926
ENSE00002487268	106558486	106558625
ENSE00002490592	106553455	106553567
ENSE00002499294	106527305	106527470
ENSE00002508542	106530176	106530315
ENSE00002530802	106541586	106541621
ENSE00002704204	106519131	106521453
ENSE00003599370	106544788	106544933
ENSE00003776258	106511430	106513039
ENSE00003777910	106360717	106361081
ENSE00003779170	106451694	106451832
ENSE00003783185	106568472	106572017
ENSE00003791112	106555768	106555897

Expression profiles

Bgee: expression breadth ubiquitous, 249 present calls, max score 99.03.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.1682 / max 219.6921, expressed in 1412 samples.

FANTOM5 promoters (20 alternative TSS)

Promoter ID	TPM avg	Samples expressed
69127	3.4019	875
69111	1.8383	365
69128	1.3567	587
69124	0.9710	434
69130	0.9534	462
69129	0.7223	374
69121	0.6885	359
69126	0.6078	326
69113	0.5125	200
69119	0.3964	223

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tongue squamous epithelium	UBERON:0006919	99.03	gold quality
esophagus squamous epithelium	UBERON:0006920	98.62	gold quality
upper leg skin	UBERON:0004262	98.12	gold quality
oral cavity	UBERON:0000167	98.09	gold quality
epithelium of esophagus	UBERON:0001976	97.83	gold quality
squamous epithelium	UBERON:0006914	97.79	gold quality
gingiva	UBERON:0001828	97.78	gold quality
pancreatic ductal cell	CL:0002079	97.72	gold quality
gingival epithelium	UBERON:0001949	97.68	gold quality
pharyngeal mucosa	UBERON:0000355	97.64	gold quality
placenta	UBERON:0001987	97.44	gold quality
mammalian vulva	UBERON:0000997	97.31	gold quality
palpebral conjunctiva	UBERON:0001812	97.18	gold quality
lower esophagus mucosa	UBERON:0035834	97.05	gold quality
skin of hip	UBERON:0001554	97.00	gold quality
ileal mucosa	UBERON:0000331	96.98	gold quality
jejunal mucosa	UBERON:0000399	96.77	gold quality
upper arm skin	UBERON:0004263	96.75	gold quality
cervix epithelium	UBERON:0004801	96.19	gold quality
penis	UBERON:0000989	95.89	gold quality
secondary oocyte	CL:0000655	95.49	gold quality
nasal cavity epithelium	UBERON:0005384	95.20	gold quality
oviduct epithelium	UBERON:0004804	94.90	gold quality
esophagus mucosa	UBERON:0002469	94.86	gold quality
colonic mucosa	UBERON:0000317	94.78	gold quality
epithelium of nasopharynx	UBERON:0001951	94.76	gold quality
mucosa of sigmoid colon	UBERON:0004993	94.58	gold quality
cervix squamous epithelium	UBERON:0006922	94.43	gold quality
oocyte	CL:0000023	94.36	gold quality
mammary duct	UBERON:0001765	94.27	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-2	yes	1609.17
E-MTAB-6701	yes	115.62
E-CURD-119	yes	38.42
E-CURD-88	yes	34.64
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CTNNB1, MYC

Literature-anchored findings (GeneRIF, showing 8)

• the structure of AIM1g1, a single betagamma-crystallin domain from the protein absent in melanoma 1, was determined (PMID:16511323)
• Absent in melanoma 1 (AIM1), an unusual member of the superfamily , contains 12 betagamma-crystallin motifs in six domains. Some of these motifs diverge considerably from the canonical motif sequence. AIM1g1, the first betagamma-crystallin domain of AIM1. (PMID:18582473)
• tumor-promoting effect of deletion in 6q21, that included genes PRDM1, ATG5 and AIM1 (PMID:19194464)
• Methylation status of AIM1 in the prostate cancer specimen may predict for time to recurrence in Gleason 3 + 4 = 7 patients undergoing prostatectomy. (PMID:22127895)
• AIM1 promoter hypermethylation was found in higher frequency (P = 0.005) in metastatic melanoma (65%) than in primary melanomas (38%). (PMID:22402438)
• AIM1, ERGIC1, and TPX2 were shown to be highly expressed especially in prostate cancer tissues, and high mRNA expression of ERGIC1 and TMED3 associated with AR and ERG oncogene expression (PMID:22761906)
• Both DNMT1 and AIM1 show maternal allele-specific methylation and paternal allele-specific transcription. (PMID:24094292)
• Single-molecule Force Spectroscopy Reveals the Calcium Dependence of the Alternative Conformations in the Native State of a betagamma-Crystallin Protein. (PMID:27378818)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	crybg1b	ENSDARG00000006060
danio_rerio	crybg1a	ENSDARG00000031782
mus_musculus	Crybg1	ENSMUSG00000019866
rattus_norvegicus	Crybg1	ENSRNOG00000025998

Paralogs (14): CRYBG3 (ENSG00000080200), CRYBB3 (ENSG00000100053), CRYBB1 (ENSG00000100122), CRYBA1 (ENSG00000108255), CRYGD (ENSG00000118231), CRYGN (ENSG00000127377), CRYGC (ENSG00000163254), CRYBA2 (ENSG00000163499), CRYGA (ENSG00000168582), CRYBG2 (ENSG00000176092), CRYGB (ENSG00000182187), CRYBA4 (ENSG00000196431), CRYGS (ENSG00000213139), CRYBB2 (ENSG00000244752)

Protein

Protein identifiers

Beta/gamma crystallin domain-containing protein 1 — Q9Y4K1 (reviewed: Q9Y4K1)

Alternative names: Absent in melanoma 1 protein

All UniProt accessions (3): A0A494C1M5, Q9Y4K1, Q96QW7

UniProt curated annotations — full annotation on UniProt →

Function. May function as suppressor of malignant melanoma. It may exert its effects through interactions with the cytoskeleton.

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

Isoforms (3)

UniProt ID	Names	Canonical?
Q9Y4K1-3	3	yes
Q9Y4K1-1	1
Q9Y4K1-2	2

RefSeq proteins (2): NP_001358171, NP_001615 (=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 (75 total): compositionally biased region 18, domain 13, strand 12, region of interest 11, sequence variant 7, modified residue 6, helix 3, splice variant 2, turn 2, chain 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
3CW3	X-RAY DIFFRACTION	1.88
6VRO	X-RAY DIFFRACTION	2.45
2DAD	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y4K1-F1	49.79	0.20

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): 483, 489, 737, 756, 892, 933

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 268 (showing top): JI_RESPONSE_TO_FSH_UP, BENPORATH_ES_WITH_H3K27ME3, MCLACHLAN_DENTAL_CARIES_UP, JAEGER_METASTASIS_DN, GOZGIT_ESR1_TARGETS_DN, VICENT_METASTASIS_UP, GAUSSMANN_MLL_AF4_FUSION_TARGETS_C_UP, MODULE_511, BOYLAN_MULTIPLE_MYELOMA_D_DN, GOLDRATH_ANTIGEN_RESPONSE, DEURIG_T_CELL_PROLYMPHOCYTIC_LEUKEMIA_DN, BOYLAN_MULTIPLE_MYELOMA_D_CLUSTER_DN, KOYAMA_SEMA3B_TARGETS_UP, RHEIN_ALL_GLUCOCORTICOID_THERAPY_UP, CHARAFE_BREAST_CANCER_BASAL_VS_MESENCHYMAL_UP

GO Biological Process (1): biological_process (GO:0008150)

GO Molecular Function (2): carbohydrate binding (GO:0030246), molecular_function (GO:0003674)

GO Cellular Component (1): cellular_component (GO:0005575)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	1

Protein interactions and networks

STRING

688 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CRYBG1	MMP11	P24347	764
CRYBG1	SIRT2	Q8IXJ6	630
CRYBG1	SIRT1	Q96EB6	496
CRYBG1	MCHR2	Q969V1	421
CRYBG1	DENND2B	P78523	411
CRYBG1	H3C1	P02295	398
CRYBG1	ACTB	P02570	397
CRYBG1	ASF1A	Q9Y294	392
CRYBG1	H3-3A	P06351	380
CRYBG1	HDAC8	Q9BY41	377
CRYBG1	H3C14	Q71DI3	376
CRYBG1	H3-5	Q6NXT2	376
CRYBG1	H3-4	Q16695	376
CRYBG1	H3-7	Q5TEC6	376
CRYBG1	HDAC3	O15379	375

IntAct

74 interactions, top by confidence:

A	B	Type	Score
KIFAP3	KIF3B	psi-mi:“MI:0914”(association)	0.900
SOCS7	NCK2	psi-mi:“MI:0914”(association)	0.670
ANXA9	PPL	psi-mi:“MI:0914”(association)	0.660
CAPZA2	CNOT1	psi-mi:“MI:0914”(association)	0.640
TBC1D22B	A2ML1	psi-mi:“MI:0914”(association)	0.530
MRPL38	DUSP14	psi-mi:“MI:0914”(association)	0.530
FBXL4	DUSP14	psi-mi:“MI:0914”(association)	0.530
PPP2R5A	AXIN1	psi-mi:“MI:0914”(association)	0.530
ZNF829	TRIM28	psi-mi:“MI:0914”(association)	0.530
SIX2	KPNB1	psi-mi:“MI:0914”(association)	0.530
CRYBG1	H2BC21	psi-mi:“MI:0915”(physical association)	0.400
CRYBG1	HNRNPK	psi-mi:“MI:0915”(physical association)	0.400
CD44	PHRF1	psi-mi:“MI:0914”(association)	0.350
GSK3A	CTNNB1	psi-mi:“MI:0914”(association)	0.350
Xpo1	IFT56	psi-mi:“MI:0914”(association)	0.350
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
CUL3	PXDNL	psi-mi:“MI:0914”(association)	0.350
CDK15	A2ML1	psi-mi:“MI:0914”(association)	0.350
PYHIN1	DUSP14	psi-mi:“MI:0914”(association)	0.350
IL31RA	DUSP14	psi-mi:“MI:0914”(association)	0.350
ZNF829	TRIM28	psi-mi:“MI:0914”(association)	0.350
CTBP1	TAF15	psi-mi:“MI:0914”(association)	0.350
ZBTB18	DNASE1L1	psi-mi:“MI:0914”(association)	0.350

BioGRID (96): AIM1 (Affinity Capture-MS), AIM1 (Affinity Capture-MS), AIM1 (Affinity Capture-MS), AIM1 (Affinity Capture-MS), AIM1 (Affinity Capture-MS), AIM1 (Affinity Capture-MS), AIM1 (Proximity Label-MS), AIM1 (Affinity Capture-MS), AIM1 (Affinity Capture-MS), AIM1 (Affinity Capture-MS), AIM1 (Affinity Capture-MS), AIM1 (Affinity Capture-MS), AIM1 (Affinity Capture-MS), AIM1 (Affinity Capture-MS), AIM1 (Affinity Capture-MS)

ESM2 similar proteins: A0A1B0GUA9, A0JNH1, A1L170, A2TJV2, A6H7B4, A6NFA0, A6NGY1, A6X8Z5, A7YY35, B2RQL2, D3Z1D3, M0RD54, P43359, Q05860, Q0VF49, Q1RMX6, Q1RN00, Q2M1Z3, Q32LI3, Q3URK1, Q5EBJ4, Q5M831, Q5RJL0, Q62100, Q640N3, Q64256, Q642A3, Q66H53, Q66LM6, Q68D20, Q68DA7, Q68US1, Q6AXN6, Q6AYA8, Q6IR42, Q711Q0, Q80VY2, Q86UF4, Q8IY42, Q8TDR4

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.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 95 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Transcriptional regulation by RUNX1	5	11.6×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	263
Likely benign	26
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

2449 predictions. Top by Δscore:

Variant	Effect	Δscore
6:106525121:A:AG	acceptor_gain	1.0000
6:106525121:ATCT:A	acceptor_gain	1.0000
6:106525122:T:G	acceptor_gain	1.0000
6:106525124:T:A	acceptor_gain	1.0000
6:106525128:TGCA:T	acceptor_loss	1.0000
6:106525129:GCAG:G	acceptor_loss	1.0000
6:106525130:CAG:C	acceptor_loss	1.0000
6:106525131:A:AG	acceptor_gain	1.0000
6:106525131:AGAC:A	acceptor_loss	1.0000
6:106525132:G:GC	acceptor_gain	1.0000
6:106525132:GAC:G	acceptor_gain	1.0000
6:106525132:GACA:G	acceptor_gain	1.0000
6:106525132:GACAC:G	acceptor_gain	1.0000
6:106525178:AAGGT:A	donor_loss	1.0000
6:106525181:G:GA	donor_loss	1.0000
6:106525263:TGCA:T	acceptor_loss	1.0000
6:106525264:GCAG:G	acceptor_loss	1.0000
6:106525265:CAGG:C	acceptor_loss	1.0000
6:106525267:GGT:G	acceptor_gain	1.0000
6:106525267:GGTA:G	acceptor_gain	1.0000
6:106525361:A:AG	donor_gain	1.0000
6:106525382:GGATG:G	donor_gain	1.0000
6:106525383:GATG:G	donor_gain	1.0000
6:106525383:GATGG:G	donor_gain	1.0000
6:106525384:ATGGT:A	donor_loss	1.0000
6:106525385:TGGTA:T	donor_loss	1.0000
6:106525387:G:GA	donor_loss	1.0000
6:106525387:G:GG	donor_gain	1.0000
6:106525388:T:A	donor_loss	1.0000
6:106527297:A:AG	acceptor_gain	1.0000

AlphaMissense

14005 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:106539404:T:A	W1166R	0.999
6:106539404:T:C	W1166R	0.999
6:106551853:T:A	W1364R	0.999
6:106551853:T:C	W1364R	0.999
6:106551931:T:A	W1390R	0.999
6:106551931:T:C	W1390R	0.999
6:106561468:T:A	W1628R	0.999
6:106561468:T:C	W1628R	0.999
6:106568540:T:A	W1716R	0.999
6:106568540:T:C	W1716R	0.999
6:106527306:T:A	W1064R	0.998
6:106527306:T:C	W1064R	0.998
6:106539408:T:C	L1167P	0.998
6:106539509:T:C	S1201P	0.998
6:106539516:G:C	R1203P	0.998
6:106544911:T:C	S1356P	0.998
6:106551962:T:A	V1400D	0.998
6:106561364:G:C	R1593P	0.998
6:106561390:T:C	S1602P	0.998
6:106561427:G:C	R1614T	0.998
6:106561427:G:T	R1614M	0.998
6:106561428:G:C	R1614S	0.998
6:106561428:G:T	R1614S	0.998
6:106561495:T:C	C1637R	0.998
6:106563860:T:A	W1671R	0.998
6:106563860:T:C	W1671R	0.998
6:106563925:A:C	K1692N	0.998
6:106563925:A:T	K1692N	0.998
6:106568542:G:C	W1716C	0.998
6:106568542:G:T	W1716C	0.998

dbSNP variants (sampled 300 via entrez): RS1000069763 (6:106437307 T>TCC), RS1000070294 (6:106395222 CCTT>C), RS1000080520 (6:106384364 A>C), RS1000100849 (6:106426320 A>G), RS1000110818 (6:106386072 G>C), RS1000116070 (6:106487090 G>A), RS1000121640 (6:106437541 ATCC>A), RS1000122990 (6:106491444 T>C), RS1000125109 (6:106565730 C>T), RS1000126748 (6:106480410 A>G), RS1000139538 (6:106552633 T>A), RS1000154007 (6:106545243 A>T), RS1000171271 (6:106513457 G>A,C,T), RS1000184601 (6:106438573 G>A), RS1000185209 (6:106407727 A>G)

Disease associations

OMIM: gene MIM:601797 | 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
GCST000032_3	Stroke	9.000000e-06
GCST008473_3	Visceral fat	1.000000e-09
GCST008473_4	Visceral fat	4.000000e-10

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066173 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

60 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	9
bisphenol A	affects cotreatment, increases methylation, decreases expression	2
sodium arsenite	decreases expression, affects methylation	2
entinostat	increases expression, affects cotreatment	2
belinostat	increases expression, affects cotreatment	2
Panobinostat	affects cotreatment, increases expression	2
Tetrachlorodibenzodioxin	decreases expression	2
Cyclosporine	decreases expression, increases expression	2
sotorasib	affects cotreatment, decreases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, decreases expression, increases expression	1
terbufos	increases methylation	1
trichostatin A	increases expression	1
hydroxyhydroquinone	increases expression	1
mono-(2-ethylhexyl)phthalate	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
butyraldehyde	increases expression	1
potassium chromate(VI)	decreases expression	1
cupric oxide	increases expression	1
S-(1,2-dichlorovinyl)cysteine	decreases expression, affects cotreatment	1
pentanal	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
licochalcone B	decreases expression	1
bisphenol S	affects cotreatment, decreases methylation	1
jinfukang	affects cotreatment, decreases expression	1
trametinib	affects cotreatment, decreases expression	1
(+)-JQ1 compound	decreases expression	1
NVP-BKM120	affects cotreatment, decreases expression	1

ChEMBL screening assays

6 unique, capped per target: 6 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5697439	Binding	Inhibition of AIM1 (unknown origin) assessed as fold change at 10 uM incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia. — Nature

Clinical trials (associated diseases)

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