GML

Summary

GML (glycosylphosphatidylinositol anchored molecule like, HGNC:4375) is a protein-coding gene on chromosome 8q24.3, encoding Glycosyl-phosphatidylinositol-anchored molecule-like protein (Q99445). May play a role in the apoptotic pathway or cell-cycle regulation induced by p53/TP53 after DNA damage.

Predicted to be involved in DNA damage response, signal transduction by p53 class mediator; apoptotic process; and negative regulation of cell population proliferation. Predicted to be located in plasma membrane. Predicted to be extrinsic component of membrane.

Source: NCBI Gene 2765 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 24 total
• Phenotypes (HPO): 1
• MANE Select transcript: NM_002066

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4375
Approved symbol	GML
Name	glycosylphosphatidylinositol anchored molecule like
Location	8q24.3
Locus type	gene with protein product
Status	Approved
Aliases	LY6DL
Ensembl gene	ENSG00000104499
Ensembl biotype	protein_coding
OMIM	602370
Entrez	2765

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000220940, ENST00000522728

RefSeq mRNA: 1 — MANE Select: NM_002066 NM_002066

CCDS: CCDS6391

Canonical transcript exons

ENST00000220940 — 4 exons

Exon	Start	End
ENSE00000862678	142846395	142846851
ENSE00001210364	142841118	142841225
ENSE00001210366	142834801	142834868
ENSE00001210373	142840416	142840510

Expression profiles

Bgee: expression breadth broad, 90 present calls, max score 99.13.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right adrenal gland cortex	UBERON:0035827	99.13	gold quality
right adrenal gland	UBERON:0001233	98.31	gold quality
left adrenal gland	UBERON:0001234	98.11	gold quality
left adrenal gland cortex	UBERON:0035825	97.60	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	95.50	gold quality
adrenal tissue	UBERON:0018303	94.44	gold quality
adrenal cortex	UBERON:0001235	93.93	gold quality
adrenal gland	UBERON:0002369	91.01	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.44	gold quality
right testis	UBERON:0004534	70.71	gold quality
left testis	UBERON:0004533	67.65	gold quality
testis	UBERON:0000473	66.22	gold quality
buccal mucosa cell	CL:0002336	65.37	gold quality
secondary oocyte	CL:0000655	61.64	gold quality
oocyte	CL:0000023	59.50	silver quality
metanephric glomerulus	UBERON:0004736	55.97	gold quality
upper leg skin	UBERON:0004262	53.38	silver quality
Brodmann (1909) area 10	UBERON:0013541	50.91	gold quality
frontal pole	UBERON:0002795	50.41	gold quality
middle frontal gyrus	UBERON:0002702	50.30	gold quality
paraflocculus	UBERON:0005351	50.18	gold quality
skin of hip	UBERON:0001554	49.54	silver quality
cerebellar vermis	UBERON:0004720	49.25	gold quality
germinal epithelium of ovary	UBERON:0001304	47.22	gold quality
endometrium epithelium	UBERON:0004811	46.85	gold quality
lower esophagus mucosa	UBERON:0035834	45.91	silver quality
quadriceps femoris	UBERON:0001377	45.21	gold quality
right coronary artery	UBERON:0001625	44.94	gold quality
vastus lateralis	UBERON:0001379	44.28	gold quality
mucosa of transverse colon	UBERON:0004991	43.70	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.63

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TP53

miRNA regulators (miRDB)

14 targeting GML, 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-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-6715A-3P	99.83	68.05	1473
HSA-MIR-7515	99.31	68.22	1795
HSA-MIR-16-2-3P	99.29	70.60	1954
HSA-MIR-195-3P	99.29	70.61	1954
HSA-MIR-3191-5P	99.24	66.52	1722
HSA-MIR-3154	98.94	66.55	1455
HSA-MIR-4726-5P	97.24	65.67	1299
HSA-MIR-125A-3P	97.04	66.92	902
HSA-MIR-552-3P	96.68	64.12	1026

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Gml	ENSMUSG00000068349
mus_musculus	Gml2	ENSMUSG00000068600
rattus_norvegicus		ENSRNOG00000072933

Paralogs (1): LY6K (ENSG00000160886)

Protein

Protein identifiers

Glycosyl-phosphatidylinositol-anchored molecule-like protein — Q99445 (reviewed: Q99445)

All UniProt accessions (2): Q99445, E5RI31

UniProt curated annotations — full annotation on UniProt →

Function. May play a role in the apoptotic pathway or cell-cycle regulation induced by p53/TP53 after DNA damage.

Subcellular location. Cell membrane.

Induction. By p53/TP53.

RefSeq proteins (1): NP_002057* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR016054	LY6_UPA_recep-like	Domain
IPR018363	CD59_antigen_CS	Conserved_site
IPR045860	Snake_toxin-like_sf	Homologous_superfamily
IPR052874	Sperm-ZP_regulatory	Family

UniProt features (9 total): disulfide bond 5, signal peptide 1, chain 1, domain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q99445-F1	76.33	0.26

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Disulfide bonds (5): 31–55, 34–42, 48–73, 77–104, 105–110

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-3371453	Regulation of HSF1-mediated heat shock response
R-HSA-3371511	HSF1 activation
R-HSA-3371568	Attenuation phase
R-HSA-3371571	HSF1-dependent transactivation

MSigDB gene sets: 70 (showing top): XU_GH1_AUTOCRINE_TARGETS_UP, GERY_CEBP_TARGETS, GOBP_DNA_DAMAGE_RESPONSE, GOBP_SIGNAL_TRANSDUCTION_BY_P53_CLASS_MEDIATOR, GOBP_SIGNAL_TRANSDUCTION_IN_RESPONSE_TO_DNA_DAMAGE, ACEVEDO_METHYLATED_IN_LIVER_CANCER_DN, GOCC_SIDE_OF_MEMBRANE, GOCC_EXTRINSIC_COMPONENT_OF_MEMBRANE, NIKOLSKY_BREAST_CANCER_8Q23_Q24_AMPLICON, GAUSSMANN_MLL_AF4_FUSION_TARGETS_G_UP, CHYLA_CBFA2T3_TARGETS_DN, chr8q24, ZWANG_TRANSIENTLY_UP_BY_2ND_EGF_PULSE_ONLY, RAPA_EARLY_UP.V1_UP, REACTOME_REGULATION_OF_HSF1_MEDIATED_HEAT_SHOCK_RESPONSE

GO Biological Process (3): apoptotic process (GO:0006915), negative regulation of cell population proliferation (GO:0008285), DNA damage response, signal transduction by p53 class mediator (GO:0030330)

GO Molecular Function (0):

GO Cellular Component (4): plasma membrane (GO:0005886), extrinsic component of membrane (GO:0019898), side of membrane (GO:0098552), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Cellular response to heat stress	3
HSF1-dependent transactivation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
membrane	3
cellular anatomical structure	3
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
cell population proliferation	1
regulation of cell population proliferation	1
negative regulation of cellular process	1
signal transduction in response to DNA damage	1
signal transduction by p53 class mediator	1
cell periphery	1
leaflet of membrane bilayer	1

Protein interactions and networks

STRING

244 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GML	LRRC40	Q9H9A6	609
GML	CNPY4	Q8N129	573
GML	LY6L	H3BQJ8	571
GML	LRIG3	Q6UXM1	548
GML	PATE3	B3GLJ2	522
GML	TP53	P04637	496
GML	LYPD4	Q6UWN0	495
GML	CNPY3	Q9BT09	481
GML	PINLYP	A6NC86	479
GML	PATE2	Q6UY27	448
GML	PATE4	P0C8F1	445
GML	LYPD5	Q6UWN5	445
GML	PNMA8B	Q9ULN7	438
GML	PATE1	Q8WXA2	435
GML	LY6G5B	Q8NDX9	417

IntAct

4 interactions, top by confidence:

A	B	Type	Score
GML	CLSTN1	psi-mi:“MI:0914”(association)	0.350
GML	ITGA8	psi-mi:“MI:0914”(association)	0.350
GML	POTEF	psi-mi:“MI:0914”(association)	0.350

BioGRID (72): EIF2A (Affinity Capture-MS), TUBA4A (Affinity Capture-MS), LSS (Affinity Capture-MS), CNTNAP3 (Affinity Capture-MS), DHFRL1 (Affinity Capture-MS), LAMA3 (Affinity Capture-MS), TUBB3 (Affinity Capture-MS), LAMB2 (Affinity Capture-MS), TMEM67 (Affinity Capture-MS), TUBA1A (Affinity Capture-MS), GBF1 (Affinity Capture-MS), FAT1 (Affinity Capture-MS), FRAS1 (Affinity Capture-MS), LRIG1 (Affinity Capture-MS), CYB5R3 (Affinity Capture-MS)

ESM2 similar proteins: A7E2Z9, B3MFC2, B3NSF6, B4GAN3, B4HNI3, B4J8Z9, B4KR21, B4LQ44, B4MQJ1, B4P641, B4QBL6, B5A5T4, B5E022, C6K2K4, D3ZTT2, O13157, O88745, O94907, P01216, P24387, P43446, P68241, P68242, Q01974, Q26492, Q5R7F5, Q5RH73, Q66IA6, Q6DGP8, Q6FHJ7, Q76KF0, Q7YRN1, Q86Y78, Q8BNJ6, Q8BPP5, Q8CGD2, Q8JIE9, Q8NC67, Q8NFY4, Q99445

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	21
Likely benign	1
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

3605 predictions. Top by Δscore:

Variant	Effect	Δscore
8:142840509:GT:G	donor_gain	1.0000
8:142840511:G:GG	donor_gain	1.0000
8:142874955:A:AC	donor_gain	1.0000
8:142874956:C:CC	donor_gain	1.0000
8:142875875:CCGT:C	acceptor_gain	1.0000
8:142875876:CGT:C	acceptor_gain	1.0000
8:142875876:CGTC:C	acceptor_gain	1.0000
8:142875878:TCTGC:T	acceptor_loss	1.0000
8:142875879:C:CA	acceptor_loss	1.0000
8:142875879:C:CC	acceptor_gain	1.0000
8:142875880:T:A	acceptor_loss	1.0000
8:142876208:CCCT:C	donor_gain	1.0000
8:142876253:C:CA	donor_gain	1.0000
8:142876266:T:TA	donor_gain	1.0000
8:142876401:C:CT	acceptor_gain	1.0000
8:142876681:CCGTA:C	donor_gain	1.0000
8:142876685:A:AC	donor_gain	1.0000
8:142876686:C:CC	donor_gain	1.0000
8:142876886:C:CC	acceptor_gain	1.0000
8:142876972:C:A	donor_gain	1.0000
8:142876983:C:CA	donor_gain	1.0000
8:142877017:CCACA:C	donor_loss	1.0000
8:142877018:CACA:C	donor_loss	1.0000
8:142877019:ACACC:A	donor_loss	1.0000
8:142877021:ACCT:A	donor_loss	1.0000
8:142877022:C:A	donor_loss	1.0000
8:142877022:CCTT:C	donor_gain	1.0000
8:142877058:T:TA	donor_gain	1.0000
8:142877218:CATTC:C	acceptor_gain	1.0000
8:142877220:TTC:T	acceptor_gain	1.0000

AlphaMissense

1046 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:142846426:G:C	K71N	0.983
8:142846426:G:T	K71N	0.983
8:142846448:T:C	F79L	0.981
8:142846450:T:A	F79L	0.981
8:142846450:T:G	F79L	0.981
8:142841162:T:C	F40L	0.971
8:142841164:C:A	F40L	0.971
8:142841164:C:G	F40L	0.971
8:142846425:A:T	K71M	0.956
8:142846508:T:C	F99L	0.954
8:142846510:C:A	F99L	0.954
8:142846510:C:G	F99L	0.954
8:142846449:T:G	F79C	0.951
8:142846546:T:A	N111K	0.950
8:142846546:T:G	N111K	0.950
8:142841163:T:G	F40C	0.944
8:142846425:A:C	K71T	0.944
8:142846424:A:G	K71E	0.942
8:142841157:A:T	N38I	0.933
8:142846541:T:A	C110S	0.933
8:142846542:G:C	C110S	0.933
8:142841205:G:C	R54P	0.931
8:142841135:T:A	C31S	0.929
8:142841136:G:C	C31S	0.929
8:142841119:G:C	W25C	0.925
8:142841119:G:T	W25C	0.925
8:142841186:T:C	C48R	0.920
8:142841220:C:T	S59F	0.919
8:142846419:T:A	V69D	0.919
8:142841220:C:A	S59Y	0.917

dbSNP variants (sampled 300 via entrez): RS1000518263 (8:142837297 T>G), RS1000529834 (8:142845319 G>A), RS1000711472 (8:142847092 A>C), RS1001164944 (8:142846840 T>C), RS1001692892 (8:142835481 A>C), RS1002120785 (8:142835336 G>A,T), RS1002247302 (8:142841360 T>G), RS1002576911 (8:142835677 A>G), RS1002691354 (8:142836706 G>A), RS1002698398 (8:142836915 T>C), RS1002839547 (8:142847136 C>T), RS1002934804 (8:142843647 A>G), RS1003118611 (8:142838761 A>G), RS1003204586 (8:142842207 A>C,T), RS1003263689 (8:142844785 C>A)

Disease associations

OMIM: gene MIM:602370 | disease phenotypes: MIM:209850

GenCC curated gene-disease

Mondo (1): autism (MONDO:0005260)

Orphanet (0):

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0000717	Autism

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST007929_52	Medication use (calcium channel blockers)	4.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009930	Calcium channel blocker use measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D001321	Autistic Disorder	F03.625.164.113.500

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

8 total (human), top 8 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases expression, affects cotreatment	2
naringenin	increases expression, affects cotreatment	1
CGP 52608	increases reaction, affects binding	1
SRT2183	increases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Quercetin	affects cotreatment, increases expression	1
Valproic Acid	increases methylation	1
Gold Compounds	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00211796	PHASE4	COMPLETED	Divalproex Sodium ER in Adult Autism
NCT00391261	PHASE4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT00409747	PHASE4	COMPLETED	Minocycline to Treat Childhood Regressive Autism
NCT00576732	PHASE4	COMPLETED	A Study of the Effectiveness and Safety of Two Doses of Risperidone in the Treatment of Children and Adolescents With Autistic Disorder
NCT00844753	PHASE4	COMPLETED	Atomoxetine, Placebo and Parent Management Training in Autism
NCT01028820	PHASE4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01098383	PHASE4	UNKNOWN	Treatment With Acetyl-Choline Esterase Inhibitors in Children With Autism Spectrum Disorders
NCT01333865	PHASE4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	PHASE4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	PHASE4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02069977	PHASE4	UNKNOWN	Study to Evaluate the Efficacy and Safety of Aripiprazole
NCT02096952	PHASE4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02199925	PHASE4	UNKNOWN	An Open-Label Study to Evaluate the Efficacy of High-Dose Gammaplex in Children on the Autism Spectrum
NCT02235467	PHASE4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02255565	PHASE4	COMPLETED	Dose Response Effects of Quillivant XR in Children With ADHD and Autism: A Pilot Study
NCT02940574	PHASE4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	PHASE4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	PHASE4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	PHASE4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	PHASE4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	PHASE4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	PHASE4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	PHASE4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	PHASE4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	PHASE4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665	PHASE4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07054697	PHASE4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	PHASE4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD
NCT07439042	PHASE4	NOT_YET_RECRUITING	Buspirone for Anxiety in Autistic Youth
NCT00036231	PHASE3	TERMINATED	Synthetic Human Secretin in Children With Autism and Gastrointestinal Dysfunction
NCT00036244	PHASE3	COMPLETED	Synthetic Human Secretin in Children With Autism
NCT00065884	PHASE3	UNKNOWN	Valproate Response in Aggressive Autistic Adolescents
NCT00065962	PHASE3	COMPLETED	Secretin for the Treatment of Autism
NCT00252603	PHASE3	COMPLETED	Galantamine Versus Placebo in Childhood Autism
NCT00346736	PHASE3	COMPLETED	Use of Acupuncture In Children With Autistic Spectrum Disorder
NCT00352248	PHASE3	COMPLETED	Randomized Controlled Trial of Acupuncture Versus Sham Acupuncture in Autistic Spectrum Disorder
NCT00352352	PHASE3	COMPLETED	Use of Acupuncture In Children With Autistic Spectrum Disorder
NCT00355329	PHASE3	COMPLETED	Randomized Control Trial of Using Tongue Acupuncture in Autistic Spectrum Disorder Using PET Scan for Clinical Correlation
NCT00498173	PHASE3	COMPLETED	Effectiveness of Atomoxetine in Treating ADHD Symptoms in Children and Adolescents With Autism
NCT00541346	PHASE3	COMPLETED	A Pilot Study of Daytrana TM in Children With Autism Co-Morbid for Attention Deficit Hyperactivity Disorder (ADHD) Symptoms