BEGAIN

Summary

BEGAIN (brain enriched guanylate kinase associated, HGNC:24163) is a protein-coding gene on chromosome 14q32.2, encoding Brain-enriched guanylate kinase-associated protein (Q9BUH8). May sustain the structure of the postsynaptic density (PSD).

Predicted to enable kinase activity. Predicted to be involved in evoked excitatory postsynaptic potential and regulation of postsynaptic neurotransmitter receptor activity. Predicted to be located in dendrite; nucleus; and presynapse. Predicted to be active in glutamatergic synapse and postsynapse.

Source: NCBI Gene 57596 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 90 total — 5 pathogenic, 1 likely-pathogenic
• MANE Select transcript: NM_001385089

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24163
Approved symbol	BEGAIN
Name	brain enriched guanylate kinase associated
Location	14q32.2
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1446
Ensembl gene	ENSG00000183092
Ensembl biotype	protein_coding
OMIM	618597
Entrez	57596

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 9 protein_coding, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000355173, ENST00000553553, ENST00000554140, ENST00000554274, ENST00000554356, ENST00000554747, ENST00000556188, ENST00000556751, ENST00000557378, ENST00000637646, ENST00000637716, ENST00000965912

RefSeq mRNA: 25 — MANE Select: NM_001385089 NM_001159531, NM_001385082, NM_001385083, NM_001385084, NM_001385085, NM_001385086, NM_001385087, NM_001385088, NM_001385089, NM_001385090, NM_001385091, NM_001385092, NM_001385093, NM_001385094, NM_001385095, NM_001385096, NM_001385097, NM_001385098, NM_001385099, NM_001385100, NM_001385101, NM_001385102, NM_001385103, NM_001385104, NM_020836

CCDS: CCDS91931, CCDS91932, CCDS91933, CCDS9962

Canonical transcript exons

ENST00000554140 — 7 exons

Exon	Start	End
ENSE00001293612	100540496	100540579
ENSE00001313178	100543858	100543965
ENSE00002469983	100587249	100587417
ENSE00003569563	100567911	100567939
ENSE00003590674	100545000	100545066
ENSE00003691835	100546501	100546662
ENSE00003799593	100537147	100539315

Expression profiles

Bgee: expression breadth ubiquitous, 181 present calls, max score 96.07.

FANTOM5 (CAGE): breadth broad, TPM avg 1.0405 / max 47.2762, expressed in 388 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
144939	0.2434	86
144946	0.1834	77
144941	0.1434	85
144943	0.1426	72
144942	0.1088	42
144945	0.1079	56
144940	0.0724	35
144944	0.0386	24

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	96.07	gold quality
cerebellar hemisphere	UBERON:0002245	95.44	gold quality
cerebellar cortex	UBERON:0002129	95.33	gold quality
cerebellum	UBERON:0002037	94.06	gold quality
right frontal lobe	UBERON:0002810	92.64	gold quality
anterior cingulate cortex	UBERON:0009835	91.86	gold quality
cingulate cortex	UBERON:0003027	91.78	gold quality
body of pancreas	UBERON:0001150	90.27	gold quality
Brodmann (1909) area 9	UBERON:0013540	89.70	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	89.57	gold quality
amygdala	UBERON:0001876	89.50	gold quality
neocortex	UBERON:0001950	88.19	gold quality
adenohypophysis	UBERON:0002196	88.16	gold quality
frontal cortex	UBERON:0001870	87.97	gold quality
cerebral cortex	UBERON:0000956	87.73	gold quality
pituitary gland	UBERON:0000007	87.49	gold quality
Ammon’s horn	UBERON:0001954	87.33	gold quality
temporal lobe	UBERON:0001871	87.21	gold quality
nucleus accumbens	UBERON:0001882	87.12	gold quality
orbitofrontal cortex	UBERON:0004167	86.99	silver quality
superior frontal gyrus	UBERON:0002661	86.98	gold quality
prefrontal cortex	UBERON:0000451	86.58	gold quality
telencephalon	UBERON:0001893	86.47	gold quality
entorhinal cortex	UBERON:0002728	86.23	gold quality
CA1 field of hippocampus	UBERON:0003881	86.12	silver quality
forebrain	UBERON:0001890	86.06	gold quality
brain	UBERON:0000955	86.05	gold quality
cortical plate	UBERON:0005343	85.82	gold quality
caudate nucleus	UBERON:0001873	85.50	gold quality
postcentral gyrus	UBERON:0002581	85.47	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.28
E-MTAB-6058	no	0.51

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

51 targeting BEGAIN, 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-5193	100.00	67.26	1744
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4500	99.99	72.72	2367
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-7162-3P	99.89	68.16	1682
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-623	99.76	68.16	1170
HSA-MIR-4755-5P	99.71	70.34	2716
HSA-MIR-5006-3P	99.71	70.26	2728
HSA-MIR-1290	99.59	69.90	2079
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-1275	99.47	67.90	2749
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-548V	99.29	69.47	1157

Literature-anchored findings (GeneRIF, showing 3)

• This study found in BEGAIN was most significant and also showed significant correlations with gene expression. (PMID:24662927)
• With the exception of associations of BEGAIN with severe and UBE3D with moderate chronic periodontitis (CP) , no other loci were associated with CP in ARIC or aggressive periodontitis in the German sample. (PMID:26962152)
• Effects of paternal and chronological age on BEGAIN methylation and its possible role in autism. (PMID:38019471)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Begain	ENSMUSG00000040867
rattus_norvegicus	Begain	ENSRNOG00000004650

Protein

Protein identifiers

Brain-enriched guanylate kinase-associated protein — Q9BUH8 (reviewed: Q9BUH8)

All UniProt accessions (8): Q9BUH8, A0A1B0GTT1, A0A1B0GVM0, G3V2K4, G3V3A2, G3V3R5, G3V3S3, G3V536

UniProt curated annotations — full annotation on UniProt →

Function. May sustain the structure of the postsynaptic density (PSD).

Subunit / interactions. Interacts with DLG4 and DLGAP1 and forms a ternary complex.

Subcellular location. Cytoplasm. Membrane.

RefSeq proteins (25): NP_001153003, NP_001372011, NP_001372012, NP_001372013, NP_001372014, NP_001372015, NP_001372016, NP_001372017, NP_001372018, NP_001372019, NP_001372020, NP_001372021, NP_001372022, NP_001372023, NP_001372024, NP_001372025, NP_001372026, NP_001372027, NP_001372028, NP_001372029, NP_001372030, NP_001372031, NP_001372032, NP_001372033, NP_065887 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR043441	Tjap1/BEGAIN	Family

UniProt features (20 total): modified residue 18, chain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BUH8-F1	57.19	0.22

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 (18): 381, 455, 465, 475, 477, 500, 502, 506, 553, 563, 1, 137, 200, 229, 246, 265, 346, 373

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-6794361	Neurexins and neuroligins
R-HSA-112316	Neuronal System
R-HSA-6794362	Protein-protein interactions at synapses

MSigDB gene sets: 98 (showing top): GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_DN, RNGTGGGC_UNKNOWN, LEE_NEURAL_CREST_STEM_CELL_DN, MODULE_255, MODULE_317, GGGTGGRR_PAX4_03, GOBP_CELL_CELL_SIGNALING, GOBP_REGULATION_OF_POSTSYNAPTIC_MEMBRANE_POTENTIAL, GOBP_SYNAPTIC_SIGNALING, AACTTT_UNKNOWN, HAMAI_APOPTOSIS_VIA_TRAIL_DN, chr14q32, GOCC_POSTSYNAPSE, GOBP_REGULATION_OF_MEMBRANE_POTENTIAL, GOCC_SYNAPSE

GO Biological Process (1): evoked excitatory postsynaptic potential (GO:0098817)

GO Molecular Function (2): protein binding (GO:0005515), kinase activity (GO:0016301)

GO Cellular Component (4): cytoplasm (GO:0005737), membrane (GO:0016020), synapse (GO:0045202), postsynapse (GO:0098794)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Protein-protein interactions at synapses	1
Neuronal System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
excitatory postsynaptic potential	1
binding	1
transferase activity, transferring phosphorus-containing groups	1
intracellular anatomical structure	1
cell junction	1
synapse	1

Protein interactions and networks

STRING

1388 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BEGAIN	MPP2	Q14168	805
BEGAIN	DLG2	Q15700	789
BEGAIN	WDR25	Q64LD2	743
BEGAIN	SLC25A29	Q8N8R3	615
BEGAIN	RTL1	A6NKG5	596
BEGAIN	DLK1	P15803	543
BEGAIN	DLG4	P78352	540
BEGAIN	GRIK2	Q13002	526
BEGAIN	TRAPPC9	Q96Q05	486
BEGAIN	GRIK5	Q16478	484
BEGAIN	CHRAC1	Q9NRG0	477
BEGAIN	TYW3	Q6IPR3	458
BEGAIN	ASB4	Q9Y574	444
BEGAIN	F11R	Q9Y624	439
BEGAIN	ANKRD34C	P0C6C1	434

IntAct

153 interactions, top by confidence:

A	B	Type	Score
PRKCZ	PRKCI	psi-mi:“MI:0914”(association)	0.890
BEGAIN	ZNF774	psi-mi:“MI:0915”(physical association)	0.720
ZNF774	BEGAIN	psi-mi:“MI:0915”(physical association)	0.720
ZNF417	BEGAIN	psi-mi:“MI:0915”(physical association)	0.670
ENKD1	BEGAIN	psi-mi:“MI:0915”(physical association)	0.670
BEGAIN	ENKD1	psi-mi:“MI:0915”(physical association)	0.670
CEP170P1	SNAPIN	psi-mi:“MI:0915”(physical association)	0.670
BEGAIN	ZNF417	psi-mi:“MI:0915”(physical association)	0.670
Haus4	HAUS5	psi-mi:“MI:0914”(association)	0.560
TCHP	BEGAIN	psi-mi:“MI:0915”(physical association)	0.560
ZNF837	BEGAIN	psi-mi:“MI:0915”(physical association)	0.560
BEGAIN	ZNF319	psi-mi:“MI:0915”(physical association)	0.560
ZNF648	BEGAIN	psi-mi:“MI:0915”(physical association)	0.560
GEM	BEGAIN	psi-mi:“MI:0915”(physical association)	0.560
FAM90A1	BEGAIN	psi-mi:“MI:0915”(physical association)	0.560
ZNF572	BEGAIN	psi-mi:“MI:0915”(physical association)	0.560
AQP1	BEGAIN	psi-mi:“MI:0915”(physical association)	0.560
PRR35	BEGAIN	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (74): ZNF774 (Two-hybrid), BEGAIN (Affinity Capture-MS), BEGAIN (Two-hybrid), HID1 (Two-hybrid), BEGAIN (Two-hybrid), BEGAIN (Two-hybrid), BEGAIN (Two-hybrid), BEGAIN (Two-hybrid), ZNF250 (Two-hybrid), CATSPER1 (Two-hybrid), BEGAIN (Two-hybrid), ZNF417 (Two-hybrid), BEGAIN (Two-hybrid), BEGAIN (Two-hybrid), BEGAIN (Two-hybrid)

ESM2 similar proteins: A2A699, A2A7S8, A2AEV7, A5PKW4, A8MVW0, F1MUS9, O14559, O15049, O88881, O95886, P60669, P97838, Q03484, Q3B8N7, Q3KP66, Q3LUD3, Q3LUD4, Q5BJT1, Q5DTT2, Q5ZLT3, Q63HR2, Q66H43, Q68EF6, Q69YU3, Q6PDH0, Q6PFD5, Q6R6L0, Q6ZVC0, Q7TN12, Q80VC9, Q86UU1, Q86WR7, Q8C7U1, Q8CGB6, Q8VC98, Q8WUF5, Q924A2, Q96EL1, Q96FS4, Q96HB5

Diamond homologs: O88881, Q5JTD0, Q68EF6, Q6R6L0, Q9BUH8, Q9DCD5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	5
Likely pathogenic	1
Uncertain significance	74
Likely benign	1
Benign	3

Top pathogenic / likely-pathogenic (6)

Variant ID	HGVS	Classification
154707	GRCh38/hg38 14q32.2-32.31(chr14:99930669-101022599)x1	Pathogenic
162009	NC_000014.9:g.100489287_100900640del411354	Pathogenic
2578330	GRCh37/hg19 14q32.2-32.31(chr14:100397006-101488936)x1	Pathogenic
3063330	GRCh37/hg19 14q32.2(chr14:100678749-101242671)x1	Pathogenic
4682848	GRCh37/hg19 14q32.2-32.31(chr14:100419086-101506214)x1	Pathogenic
625815	GRCh37/hg19 14q32.2-32.31(chr14:99737888-101847855)	Likely pathogenic

SpliceAI

1825 predictions. Top by Δscore:

Variant	Effect	Δscore
14:100539322:CGGG:C	acceptor_gain	1.0000
14:100539328:C:CT	acceptor_gain	1.0000
14:100539329:G:T	acceptor_gain	1.0000
14:100540577:CTC:C	acceptor_gain	1.0000
14:100540578:TCC:T	acceptor_loss	1.0000
14:100540580:C:CC	acceptor_gain	1.0000
14:100540581:T:G	acceptor_loss	1.0000
14:100543856:A:AC	donor_gain	1.0000
14:100543857:C:CC	donor_gain	1.0000
14:100543964:CC:C	acceptor_gain	1.0000
14:100543965:CC:C	acceptor_gain	1.0000
14:100543979:A:T	acceptor_gain	1.0000
14:100545066:CCTGG:C	acceptor_gain	1.0000
14:100546497:TCA:T	donor_loss	1.0000
14:100546500:CCTGC:C	donor_loss	1.0000
14:100567907:TCACC:T	donor_loss	1.0000
14:100567908:CACCT:C	donor_loss	1.0000
14:100539314:AG:A	acceptor_gain	0.9900
14:100539325:G:C	acceptor_gain	0.9900
14:100539325:G:GC	acceptor_gain	0.9900
14:100539341:G:T	acceptor_gain	0.9900
14:100540491:GTTA:G	donor_loss	0.9900
14:100540492:TTA:T	donor_loss	0.9900
14:100540493:TACCT:T	donor_loss	0.9900
14:100540494:A:T	donor_loss	0.9900
14:100540495:C:CA	donor_loss	0.9900
14:100540575:AGCTC:A	acceptor_gain	0.9900
14:100540578:TC:T	acceptor_gain	0.9900
14:100540579:CC:C	acceptor_gain	0.9900
14:100543784:C:CA	donor_gain	0.9900

AlphaMissense

3970 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:100543893:C:G	A106P	1.000
14:100543901:A:G	L103P	1.000
14:100546549:A:G	L43P	1.000
14:100543913:A:G	L99P	0.999
14:100545022:A:G	L74P	0.999
14:100546507:A:G	L57P	0.999
14:100537985:C:T	G589E	0.998
14:100543871:A:G	L113P	0.998
14:100546528:A:G	L50P	0.998
14:100546541:C:G	A46P	0.998
14:100546561:A:G	L39P	0.998
14:100546603:A:G	L25P	0.998
14:100546624:A:G	L18P	0.998
14:100538006:A:T	L582H	0.997
14:100538008:G:C	S581R	0.997
14:100538008:G:T	S581R	0.997
14:100538010:T:G	S581R	0.997
14:100543913:A:T	L99H	0.997
14:100545010:A:G	L78P	0.997
14:100546570:C:G	R36P	0.997
14:100546581:G:C	F32L	0.997
14:100546581:G:T	F32L	0.997
14:100546583:A:G	F32L	0.997
14:100546594:A:G	L28P	0.997
14:100537979:A:G	L591S	0.996
14:100537985:C:A	G589V	0.996
14:100537986:C:G	G589R	0.996
14:100537986:C:T	G589R	0.996
14:100537999:C:A	K584N	0.996
14:100537999:C:G	K584N	0.996

dbSNP variants (sampled 300 via entrez): RS1000098658 (14:100549223 A>G), RS1000160873 (14:100570029 G>C), RS1000190100 (14:100586915 G>C), RS1000293963 (14:100552215 C>G), RS1000295895 (14:100553974 G>A), RS1000454711 (14:100583929 C>A), RS1000467444 (14:100575681 C>T), RS1000468418 (14:100546855 C>G,T), RS1000559436 (14:100542959 T>C), RS1000564437 (14:100570278 G>T), RS1000603472 (14:100552404 C>G), RS1000718244 (14:100565500 GTCCCA>G), RS1000758025 (14:100580777 CA>C), RS1000837546 (14:100543296 T>A,C,G), RS1000928255 (14:100537824 G>T)

Disease associations

OMIM: gene MIM:618597 | disease phenotypes: MIM:608149, MIM:616222

GenCC curated gene-disease

Mondo (2): paternal uniparental disomy of chromosome 14 (MONDO:0011975), motor developmental delay due to 14q32.2 paternally expressed gene defect (MONDO:0014541)

Orphanet (3): Kagami-Ogata syndrome (Orphanet:254519), Kagami-Ogata syndrome due to paternal uniparental disomy of chromosome 14 (Orphanet:96334), Temple syndrome (Orphanet:254516)

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST000880_19	Menarche (age at onset)	1.000000e-08
GCST007576_83	Chronotype	5.000000e-13
GCST009391_992	Metabolite levels	6.000000e-06
GCST010002_160	Refractive error	3.000000e-10

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004703	age at menarche
EFO:0008328	chronotype measurement
EFO:0010475	deoxycholate measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C536471	Uniparental disomy, paternal, chromosome 14 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

27 total (human), top 27 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Panobinostat	affects cotreatment, decreases expression	2
Benzo(a)pyrene	affects methylation, increases methylation	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Tretinoin	decreases expression, increases expression	2
Valproic Acid	decreases expression, increases methylation	2
FR900359	decreases phosphorylation	1
ethyl-p-hydroxybenzoate	decreases expression	1
benzo(e)pyrene	decreases methylation	1
coumarin	increases phosphorylation	1
beta-methylcholine	affects expression	1
pentanal	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	affects cotreatment, decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Arsenic	affects methylation	1
Cisplatin	affects cotreatment, decreases expression	1
Estradiol	increases expression	1
Methapyrilene	decreases methylation	1
Thiram	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tunicamycin	decreases expression	1
Aflatoxin B1	decreases methylation	1
Asbestos, Serpentine	increases expression	1
Antirheumatic Agents	decreases expression	1
Thapsigargin	decreases expression	1

Clinical trials (associated diseases)

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