LYSET

protein-coding

lysosomal enzyme trafficking factor

Gene summary

Involved in lysosomal transport; lysosome organization; and regulation of vesicle-mediated transport. Located in Golgi cisterna. [provided by Alliance of Genome Resources, Jul 2025]

Previous symbols:

C14orf109
TMEM251

MANE transcript

NM_001098621.4

Inheritance

ClinVar variants

P:5U:23B:2

Top phenotype

Dysostosis multiplex, Ain-Naz type

gnomAD constraint

pLI —, LoF o/e 0.61

Max pathogenic AF

—

Genomic locus

chr14:93,184,951-93,188,463

External References & Databases

Ensembl (ENSG00000153485)

Transcript & Mutation Effects

hg38 • Region Span ~3.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

dysostosis multiplex, Ain-Naz typeMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0859156

Submitter: PanelApp Australia

dysostosis multiplex, Ain-Naz typeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0859156

Submitter: G2P

dysostosis multiplex, Ain-Naz typeLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0859156

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Dysostosis multiplex, Ain-Naz typeAR

Manifestation: Craniofacial; Musculoskeletal

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: 33252156

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to LYSET variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 23

Dysostosis multiplex, Ain-Naz typeTotal: 3

LYSET-related disorderTotal: 1

Intellectual disabilityTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001098621.4. 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						0
missense	1 clinvar		23 clinvar	2 clinvar		26
nonsense		2 clinvar				2
start loss						0
frameshift		2 clinvar				2
splice donor/acceptor (+/-2bp)						0
Total	1	4	23	2	0	30

Highest pathogenic variant AF is 0.0000027368728

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 14 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001098621.4	RefSeq	NP_001092091.2	2	MANE Select
ENST00000415050.3	Ensembl	ENSP00000388431.3	2	MANE Select
NM_015676.3	RefSeq	NP_056491.1	1	Standard
ENST00000283534.4	Ensembl	ENSP00000283534.4	1	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Cellular Component

integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000415050
Coding exons: 2
Length: 2139
Individuals with no LoFs: 124776
Homozygous LoFs: 0
Heterozygous LoFs: 19
Defined: 124795
p: 0.0000761

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.940	66	91.3	0.723	0.00000449	1093
Missense (PolyPhen)		31	39.59	0.78302		470
Synonymous	1.06	25	32.7	0.764	0.00000151	326
Loss of Function	0.931	4	6.58	0.608	2.76e-7	89

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000056	0.000056	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00014	0.00014	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Intolerance Scores

RVIS EVS: 0.57
RVIS percentile EVS: 81.89

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N

Gene Damage Prediction

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