GAL

protein-coding

galanin and GMAP prepropeptide, the group of Neuropeptides

Gene summary

This gene encodes a neuroendocrine peptide that is widely expressed in the central and peripheral nervous systems and also the gastrointestinal tract, pancreas, adrenal gland and urogenital tract. The encoded protein is a precursor that is proteolytically processed to generate two mature peptides: galanin and galanin message-associated peptide (GMAP). Galanin has diverse physiological functions including nociception, feeding and energy homeostasis, osmotic regulation and water balance. GMAP has been demonstrated to possess antifungal activity and hypothesized to be part of the innate immune system. [provided by RefSeq, Jul 2015]

Previous symbols:

GALN

MANE transcript

NM_015973.5

Inheritance

ClinVar variants

P:1U:44B:18

Top phenotype

Epilepsy, familial temporal lobe, 8

gnomAD constraint

pLI —, LoF o/e 1.04

Max pathogenic AF

—

Genomic locus

chr11:68,683,779-68,691,175

External References & Databases

Ensembl (ENSG00000069482)

Transcript & Mutation Effects

hg38 • Region Span ~7.4 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

familial temporal lobe epilepsy 8LIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0014650

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Epilepsy, familial temporal lobe, 8AD

Manifestation: Neurologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 25691535

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to GAL variants in ClinVar

4 Conditions Cataloged

Familial temporal lobe epilepsy 8Total: 52

not specifiedTotal: 23

not providedTotal: 8

GAL-related disorderTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_015973.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	12 clinvar		14
missense	1 clinvar		37 clinvar	3 clinvar	3 clinvar	44
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	1	0	44	15	3	63

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 24 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_015973.5	RefSeq	NP_057057.2	5	MANE Select
ENST00000265643.4	Ensembl	ENSP00000265643.3	5	MANE Select
ENST00000933453.1	Ensembl	ENSP00000603512.1	5	Standard
ENST00000933454.1	Ensembl	ENSP00000603513.1	4	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
galn	Danio rerio	Structure: dorsal root ganglion Quality: decreased amount abnormal

Gene / Model

Organism

Observed Phenotype

galn

Danio rerio

Structure: dorsal root ganglion

Quality: decreased amount

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Signaling by GPCR
Signal Transduction
GPCR signaling-G alpha q
GPCR signaling-cholera toxin
GPCR signaling-pertussis toxin

Biological Process

inflammatory response
G protein-coupled receptor signaling pathway
neuropeptide signaling pathway
nervous system development
feeding behavior

Molecular Function

galanin receptor activity
neuropeptide hormone activity
protein binding
type 1 galanin receptor binding
type 2 galanin receptor binding

Cellular Component

extracellular region
extracellular space
Golgi apparatus
secretory granule
neuronal cell body

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000265643
Coding exons: 5
Length: 7397
Individuals with no LoFs: 125698
Homozygous LoFs: 0
Heterozygous LoFs: 39
Defined: 125737
p: 0.000155

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.0691	82	80.3	1.02	0.00000513	775
Missense (PolyPhen)		23	26.006	0.88442		275
Synonymous	-0.472	40	36.4	1.10	0.00000235	259
Loss of Function	-0.0910	8	7.73	1.04	5.05e-7	68

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00031	0.00031	rare
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0.00093	0.00089	rare
East Asian	0.00033	0.00033	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000066	0.000062	rare
South Asian	0.00026	0.00026	rare
Other	0.00017	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Endocrine hormone of the central and peripheral nervous systems that binds and activates the G protein-coupled receptors GALR1, GALR2, and GALR3. This small neuropeptide may regulate diverse physiologic functions including contraction of smooth muscle of the gastrointestinal and genitourinary tract, growth hormone and insulin release and adrenal secretion. {ECO:0000269|PubMed:1370155, ECO:0000269|PubMed:1722333, ECO:0000269|PubMed:25691535}.;
Disease: DISEASE: Epilepsy, familial temporal lobe, 8 (ETL8) [MIM:616461]: A focal form of epilepsy characterized by recurrent seizures that arise from foci within the temporal lobe. Seizures are usually accompanied by sensory symptoms, most often auditory in nature. {ECO:0000269|PubMed:25691535}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.425

Intolerance Scores

LoFtool: 0.761
RVIS EVS: 0.81
RVIS percentile EVS: 87.82

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.265

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium