GCSAML

Summary

GCSAML (germinal center associated signaling and motility like, HGNC:29583) is a protein-coding gene on chromosome 1q44, encoding Germinal center-associated signaling and motility-like protein (Q5JQS6).

This gene encodes a protein thought to be a signaling molecule associated with germinal centers, the sites of proliferation and differentiation of mature B lymphocytes. Alternate splicing results in multiple transcript variants.

Source: NCBI Gene 148823 — RefSeq curated summary.

At a glance

• GWAS associations: 25
• Clinical variants (ClinVar): 71 total — 1 pathogenic
• MANE Select transcript: NM_145278

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29583
Approved symbol	GCSAML
Name	germinal center associated signaling and motility like
Location	1q44
Locus type	gene with protein product
Status	Approved
Aliases	FLJ44728
Ensembl gene	ENSG00000169224
Ensembl biotype	protein_coding
Entrez	148823

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 10 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000366488, ENST00000366489, ENST00000366491, ENST00000463359, ENST00000526896, ENST00000527084, ENST00000527541, ENST00000529512, ENST00000531662, ENST00000536561, ENST00000623578

RefSeq mRNA: 7 — MANE Select: NM_145278 NM_001281834, NM_001281835, NM_001281836, NM_001281837, NM_001281838, NM_001281853, NM_145278

CCDS: CCDS1635, CCDS60470, CCDS73058

Canonical transcript exons

ENST00000366488 — 5 exons

Exon	Start	End
ENSE00001441828	247574143	247577690
ENSE00001742146	247565931	247565959
ENSE00002186018	247549134	247549220
ENSE00003502756	247556407	247556466
ENSE00003681324	247563590	247563639

Expression profiles

Bgee: expression breadth ubiquitous, 149 present calls, max score 92.46.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 15.9501 / max 14238.0199, expressed in 139 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
9621	12.9400	121
9620	2.3057	48
9622	0.3533	27
9619	0.1710	34
9618	0.0885	11
9616	0.0251	13
202043	0.0238	8
9617	0.0163	6
202044	0.0148	5
9613	0.0079	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	92.46	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.79	gold quality
monocyte	CL:0000576	74.96	gold quality
leukocyte	CL:0000738	74.03	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	70.27	gold quality
right testis	UBERON:0004534	69.57	gold quality
left testis	UBERON:0004533	69.27	gold quality
testis	UBERON:0000473	68.64	gold quality
cerebellar hemisphere	UBERON:0002245	68.21	gold quality
cerebellar cortex	UBERON:0002129	68.13	gold quality
cerebellum	UBERON:0002037	67.62	gold quality
bone marrow cell	CL:0002092	65.94	silver quality
prostate gland	UBERON:0002367	65.24	gold quality
right hemisphere of cerebellum	UBERON:0014890	64.29	gold quality
gall bladder	UBERON:0002110	64.16	gold quality
smooth muscle tissue	UBERON:0001135	62.66	gold quality
rectum	UBERON:0001052	62.26	gold quality
colonic epithelium	UBERON:0000397	61.49	gold quality
vermiform appendix	UBERON:0001154	59.69	gold quality
lower esophagus muscularis layer	UBERON:0035833	57.91	gold quality
lower esophagus	UBERON:0013473	57.86	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	57.52	gold quality
blood	UBERON:0000178	56.72	gold quality
upper lobe of left lung	UBERON:0008952	56.39	gold quality
right lung	UBERON:0002167	55.89	gold quality
upper lobe of lung	UBERON:0008948	55.89	gold quality
cerebellar vermis	UBERON:0004720	55.74	gold quality
caecum	UBERON:0001153	55.41	gold quality
cortical plate	UBERON:0005343	54.67	silver quality
right coronary artery	UBERON:0001625	54.12	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-HCAD-29	yes	3173.49
E-MTAB-6678	yes	697.48
E-ANND-3	yes	16.01
E-MTAB-9067	yes	11.53
E-GEOD-130148	yes	7.47
E-HCAD-10	yes	7.01
E-MTAB-9801	yes	6.33
E-CURD-112	no	2.95

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

118 targeting GCSAML, 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-6798-5P	100.00	65.77	699
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-6508-5P	99.92	70.67	2465

Literature-anchored findings (GeneRIF, showing 1)

• Maternal 5mCpG imprints at the GCSAML somatic (secondary) differentially methylated region (iDMR) are decoupled from parent-of-origin expression effects in multiple human tissues. Despite the constitutive methylation asymmetry observed for the parental alleles at the iDMR, GCSAML was expressed biallelically in five tissues: visceral adipose tissue, brain - cerebellar hemisphere, brain cerebellum, prostate, and testis. (PMID:29545821)

Cross-species orthologs

0 orthologs

Paralogs (1): GCSAM (ENSG00000174500)

Protein

Protein identifiers

Germinal center-associated signaling and motility-like protein — Q5JQS6 (reviewed: Q5JQS6)

All UniProt accessions (4): Q5JQS6, E9PLW0, E9PR51, E9PRX8

Isoforms (2)

UniProt ID	Names	Canonical?
Q5JQS6-1	1	yes
Q5JQS6-2	2

RefSeq proteins (7): NP_001268763, NP_001268764, NP_001268765, NP_001268766, NP_001268767, NP_001268782, NP_660321* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR031364	GC_assoc_lym	Family

Pfam: PF15666

UniProt features (6 total): compositionally biased region 2, chain 1, region of interest 1, coiled-coil region 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5JQS6-F1	66.66	0.01

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 69 (showing top): GOBP_REGULATION_OF_B_CELL_RECEPTOR_SIGNALING_PATHWAY, GOBP_REGULATION_OF_ANTIGEN_RECEPTOR_MEDIATED_SIGNALING_PATHWAY, GOBP_ANTIGEN_RECEPTOR_MEDIATED_SIGNALING_PATHWAY, GOBP_REGULATION_OF_LEUKOCYTE_MIGRATION, GOBP_REGULATION_OF_MONONUCLEAR_CELL_MIGRATION, GOBP_LEUKOCYTE_MIGRATION, GOBP_REGULATION_OF_IMMUNE_RESPONSE, GOBP_LYMPHOCYTE_MIGRATION, chr1q44, GOBP_B_CELL_RECEPTOR_SIGNALING_PATHWAY, GOBP_REGULATION_OF_LYMPHOCYTE_MIGRATION, GOBP_ACTIVATION_OF_IMMUNE_RESPONSE, WIERENGA_STAT5A_TARGETS_DN, GOBP_IMMUNE_RESPONSE_REGULATING_SIGNALING_PATHWAY, GOBP_MONONUCLEAR_CELL_MIGRATION

GO Biological Process (2): regulation of B cell receptor signaling pathway (GO:0050855), regulation of lymphocyte migration (GO:2000401)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
B cell receptor signaling pathway	1
regulation of antigen receptor-mediated signaling pathway	1
regulation of mononuclear cell migration	1
lymphocyte migration	1
binding	1

Protein interactions and networks

STRING

334 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GCSAML	SEZ6L	Q9BYH1	531
GCSAML	SAMD12	Q8N8I0	489
GCSAML	CALHM3	Q86XJ0	477
GCSAML	MTMR8	Q96EF0	438
GCSAML	OR2C3	Q8N628	432
GCSAML	ZNF71	Q9NQZ8	429
GCSAML	E9PNW1	E9PNW1	419
GCSAML	PTPRE	P23469	417
GCSAML	DHRS13	Q6UX07	413
GCSAML	CSTPP1	Q9H6J7	400
GCSAML	CLVS1	Q8IUQ0	396
GCSAML	CCDC71L	Q8N9Z2	396
GCSAML	TMTC2	Q8N394	375
GCSAML	KLHDC8B	Q8IXV7	373
GCSAML	GAL3ST4	Q96RP7	370
GCSAML	LONRF3	Q496Y0	370

IntAct

23 interactions, top by confidence:

A	B	Type	Score
PRKAB2	GCSAML	psi-mi:“MI:0915”(physical association)	0.560
STAMBPL1	GCSAML	psi-mi:“MI:0915”(physical association)	0.560
GCSAML	NTAQ1	psi-mi:“MI:0915”(physical association)	0.560
GCSAML	EAF1	psi-mi:“MI:0915”(physical association)	0.560
GCSAML	STAMBPL1	psi-mi:“MI:0915”(physical association)	0.560
GCSAML	UBL5	psi-mi:“MI:0915”(physical association)	0.560
GCSAML	EIF1AD	psi-mi:“MI:0915”(physical association)	0.560
GCSAML	FAM90A1	psi-mi:“MI:0915”(physical association)	0.560
GCSAML	SPAG9	psi-mi:“MI:0914”(association)	0.350
NTAQ1	GCSAML	psi-mi:“MI:0915”(physical association)	0.000
EAF1	GCSAML	psi-mi:“MI:0915”(physical association)	0.000
UBL5	GCSAML	psi-mi:“MI:0915”(physical association)	0.000
EIF1AD	GCSAML	psi-mi:“MI:0915”(physical association)	0.000
FAM90A1	GCSAML	psi-mi:“MI:0915”(physical association)	0.000
GCSAML	EIF1AD	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (12): GCSAML (Two-hybrid), GCSAML (Two-hybrid), GCSAML (Two-hybrid), GCSAML (Two-hybrid), FAM90A1 (Two-hybrid), EIF1AD (Two-hybrid), UBL5 (Two-hybrid), SASS6 (Affinity Capture-MS), PLXDC2 (Affinity Capture-MS), MARS2 (Affinity Capture-MS), SPAG9 (Affinity Capture-MS), ZMYM6 (Affinity Capture-MS)

ESM2 similar proteins: A0JNM1, D3Z1Q2, P16871, P20963, P24161, P29329, P59773, Q16655, Q29102, Q2KIP5, Q2YDG7, Q3SYX1, Q3U1F9, Q3UU41, Q3UU67, Q4W815, Q5DTU0, Q5E9I3, Q5JQS6, Q6ITQ4, Q6PF55, Q6PIZ9, Q6RFH4, Q6UWF3, Q6XQ84, Q6ZUJ8, Q6ZWK4, Q80VH0, Q80WK2, Q86UW2, Q8C115, Q8C4Q9, Q8CB93, Q8N292, Q8N4X5, Q8N6F7, Q8NDB2, Q8NEA5, Q90479, Q90VY2

Diamond homologs: Q5JQS6, Q6RFH4, Q8N6F7

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	63
Likely benign	1
Benign	1

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
253547	GRCh37/hg19 1q43-44(chr1:243103401-249119318)x1	Pathogenic

SpliceAI

1595 predictions. Top by Δscore:

Variant	Effect	Δscore
1:247507229:GCTGG:G	donor_gain	1.0000
1:247507232:GG:G	donor_gain	1.0000
1:247507233:GG:G	donor_gain	1.0000
1:247556392:T:G	acceptor_gain	1.0000
1:247556392:T:TA	acceptor_gain	1.0000
1:247556402:T:G	acceptor_gain	1.0000
1:247556405:A:AG	acceptor_gain	1.0000
1:247556406:G:GA	acceptor_gain	1.0000
1:247556406:GTT:G	acceptor_gain	1.0000
1:247556463:AACGG:A	donor_loss	1.0000
1:247556464:ACGG:A	donor_loss	1.0000
1:247556465:CGGT:C	donor_loss	1.0000
1:247556466:GGTA:G	donor_loss	1.0000
1:247556467:G:GG	donor_gain	1.0000
1:247556468:T:TC	donor_loss	1.0000
1:247563586:GTA:G	acceptor_loss	1.0000
1:247563588:A:AG	acceptor_gain	1.0000
1:247563589:G:GA	acceptor_loss	1.0000
1:247563589:G:GG	acceptor_gain	1.0000
1:247563589:GGCA:G	acceptor_gain	1.0000
1:247563635:GAAAA:G	donor_gain	1.0000
1:247563636:AAAA:A	donor_gain	1.0000
1:247563637:AAA:A	donor_gain	1.0000
1:247563638:AA:A	donor_gain	1.0000
1:247563639:AGTAA:A	donor_loss	1.0000
1:247563640:G:GG	donor_gain	1.0000
1:247563641:T:G	donor_loss	1.0000
1:247565921:A:AG	acceptor_gain	1.0000
1:247507230:CTGG:C	donor_gain	0.9900
1:247507230:CTGGG:C	donor_loss	0.9900

AlphaMissense

897 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:247574302:T:C	Y110H	0.975
1:247574303:A:C	Y110S	0.967
1:247574179:T:G	Y69D	0.956
1:247574247:C:A	N91K	0.954
1:247574247:C:G	N91K	0.954
1:247574302:T:G	Y110D	0.951
1:247574305:G:C	A111P	0.948
1:247574303:A:G	Y110C	0.946
1:247549195:G:A	G2R	0.922
1:247549195:G:C	G2R	0.922
1:247574302:T:A	Y110N	0.915
1:247574243:A:T	E90V	0.914
1:247574179:T:A	Y69N	0.912
1:247574309:T:C	L112P	0.909
1:247574239:T:C	Y89H	0.907
1:247574240:A:C	Y89S	0.902
1:247574239:T:G	Y89D	0.901
1:247574179:T:C	Y69H	0.900
1:247574180:A:C	Y69S	0.894
1:247574297:C:T	T108I	0.894
1:247574244:G:C	E90D	0.883
1:247574244:G:T	E90D	0.883
1:247574246:A:T	N91I	0.883
1:247574306:C:A	A111D	0.883
1:247574189:T:G	I72S	0.880
1:247549196:G:T	G2V	0.873
1:247574243:A:C	E90A	0.856
1:247574312:T:C	L113P	0.854
1:247574246:A:C	N91T	0.851
1:247574189:T:A	I72N	0.845

dbSNP variants (sampled 300 via entrez): RS1000005905 (1:247531025 G>C,T), RS1000103261 (1:247566238 TTTTA>T,TTTTATTTA), RS1000125380 (1:247521393 C>T), RS1000196447 (1:247554026 C>T), RS1000236980 (1:247524698 T>G), RS1000317203 (1:247510095 A>G), RS1000375794 (1:247561063 C>T), RS1000392243 (1:247560718 T>A,C), RS1000426751 (1:247556723 G>A,C), RS1000486732 (1:247513286 TC>T), RS1000509842 (1:247519696 T>C), RS1000591061 (1:247508815 G>A), RS1000602193 (1:247568461 G>A,T), RS1000610833 (1:247526153 T>G), RS1000622063 (1:247509061 G>C,T)

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

25 associations (top):

Study	Trait	p-value
GCST004599_265	Mean platelet volume	3.000000e-54
GCST004599_266	Mean platelet volume	1.000000e-60
GCST004603_202	Platelet count	2.000000e-54
GCST004603_203	Platelet count	3.000000e-86
GCST004607_210	Plateletcrit	9.000000e-23
GCST004607_211	Plateletcrit	4.000000e-43
GCST004616_123	Platelet distribution width	1.000000e-47
GCST004616_124	Platelet distribution width	5.000000e-75
GCST004619_63	Reticulocyte fraction of red cells	8.000000e-15
GCST004622_143	Reticulocyte count	1.000000e-17
GCST006101_11	Cardiometabolic and hematological traits	3.000000e-34
GCST010122_2	Ceramide levels (C22:0)	6.000000e-06
GCST90002385_111	High light scatter reticulocyte count	2.000000e-11
GCST90002392_260	Mean corpuscular volume	5.000000e-11
GCST90002395_513	Mean platelet volume	4.000000e-59
GCST90002395_514	Mean platelet volume	2.000000e-131
GCST90002397_758	Mean spheric corpuscular volume	4.000000e-17
GCST90002400_549	Plateletcrit	1.000000e-13
GCST90002400_550	Plateletcrit	1.000000e-61
GCST90002401_411	Platelet distribution width	1.000000e-50
GCST90002401_412	Platelet distribution width	7.000000e-134
GCST90002402_270	Platelet count	8.000000e-42
GCST90002402_271	Platelet count	1.000000e-151
GCST90002405_103	Reticulocyte count	1.000000e-20
GCST90002406_125	Reticulocyte fraction of red cells	7.000000e-18

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004309	platelet count
EFO:0007985	platelet crit
EFO:0007984	platelet component distribution width
EFO:0007986	reticulocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

10 total (human), top 10 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects methylation, affects cotreatment, increases methylation	1
di-n-butylphosphoric acid	affects expression	1
bisphenol S	affects cotreatment, increases methylation, decreases methylation	1
Fulvestrant	affects cotreatment, increases methylation	1
Benzo(a)pyrene	affects methylation	1
Hydralazine	increases expression, affects cotreatment	1
Methotrexate	increases expression	1
Niclosamide	decreases expression	1
Valproic Acid	increases expression, affects cotreatment	1
Aflatoxin B1	increases methylation	1

Clinical trials (associated diseases)

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