UFM1

ubiquitin fold modifier 1

Basic information

Region (hg38): 13:38349849-38363619

Previous symbols: [ "C13orf20" ]

Links

ENSG00000120686 ∙ NCBI:51569 ∙ OMIM:610553 ∙ HGNC:20597 ∙ Uniprot:P61960 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hypomyelinating leukodystrophy 6 (Supportive), mode of inheritance: AD
• leukodystrophy, hypomyelinating, 14 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Leukodystrophy, hypomyelinating, 14	AR	General	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	Craniofacial; Neurologic; Ophthalmologic	27545674; 28931644; 29868776

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the UFM1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the UFM1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				4		4
missense			7			7
nonsense						0
start loss		1				1
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			8	8	4	20
Total	0	1	15	12	4

Variants in UFM1

This is a list of pathogenic ClinVar variants found in the UFM1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
13-38349920-A-G		Leukodystrophy, hypomyelinating, 14	Likely pathogenic (Oct 21, 2022)
13-38349922-G-A		Congenital long QT syndrome	Likely pathogenic (-)
13-38349925-A-C		UFM1-related disorder	Likely benign (Feb 27, 2019)
13-38349946-A-T		Leukodystrophy, hypomyelinating, 14	Benign (Dec 05, 2021)
13-38350046-C-T		UFM1-related disorder	Likely benign (Jun 12, 2019)
13-38350047-G-A			Likely benign (Feb 01, 2024)
13-38350124-G-A			Uncertain significance (Jan 02, 2024)
13-38350126-T-C			Benign (Jan 31, 2024)
13-38350126-T-G			Likely benign (Jun 21, 2023)
13-38350130-C-T			Uncertain significance (Nov 22, 2022)
13-38350132-A-G			Likely benign (Mar 08, 2022)
13-38350145-C-G			Uncertain significance (Nov 23, 2021)
13-38350148-A-C			Uncertain significance (Mar 16, 2022)
13-38350154-C-T			Uncertain significance (May 28, 2024)
13-38350159-C-T			Likely benign (Jul 03, 2022)
13-38350164-C-T			Uncertain significance (Sep 17, 2021)
13-38350167-C-T			Uncertain significance (Aug 04, 2023)
13-38350173-C-CT			Uncertain significance (Dec 07, 2023)
13-38350245-A-G			Likely benign (Nov 19, 2024)
13-38354254-A-G			Likely benign (Nov 02, 2023)
13-38358073-T-A		Leukodystrophy, hypomyelinating, 14	Benign/Likely benign (Jan 29, 2025)
13-38358074-T-A			Likely benign (Mar 24, 2023)
13-38358075-T-A			Likely benign (May 03, 2022)
13-38358113-A-C			Likely benign (Aug 01, 2024)
13-38358115-G-A		Leukodystrophy, hypomyelinating, 14	Uncertain significance (Nov 01, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
UFM1	protein_coding	protein_coding	ENST00000239878	6	13155

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.157	0.782	125742	0	5	125747	0.0000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.617	33	44.6	0.740	0.00000230	537
Missense in Polyphen		8	10.154	0.78786		147
Synonymous	0.491	13	15.5	0.841	6.98e-7	177
Loss of Function	1.53	2	6.07	0.330	2.57e-7	79

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000295	0.0000295
Ashkenazi Jewish	0.0000996	0.0000992
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000176	0.0000176
Middle Eastern	0.00	0.00
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Ubiquitin-like modifier which can be covalently attached via an isopeptide bond to substrate proteins as a monomer or a lysine-linked polymer (PubMed:15071506, PubMed:20018847). The so- called ufmylation, requires the UFM1-activating E1 enzyme UBA5, the UFM1-conjugating E2 enzyme UFC1, and the UFM1-ligase E3 enzyme UFL1 (PubMed:15071506, PubMed:20018847). This post-translational modification on lysine residues of proteins may play a crucial role in a number of cellular processes (PubMed:15071506, PubMed:20018847). TRIP4 ufmylation may for instance play a role in nuclear receptors-mediated transcription (PubMed:25219498). Other substrates may include DDRGK1 with which it may play a role in the cellular response to endoplasmic reticulum stress (Probable). {ECO:0000269|PubMed:15071506, ECO:0000269|PubMed:20018847, ECO:0000269|PubMed:25219498, ECO:0000305|PubMed:23152784}.
• Disease: DISEASE: Leukodystrophy, hypomyelinating, 14 (HLD14) [MIM:617899]: An autosomal recessive, severe disorder characterized by atrophy of the basal ganglia and cerebellum, hypomyelination, severe developmental delay, typically without intentional movements and language development, and microcephaly. Almost all patients exhibit spasticity, extrapyramidal movement abnormalities, and severe drug-resistant epilepsy. Disease onset is early in infancy, and most patients die in the first years of life. {ECO:0000269|PubMed:28931644}. Note=The disease is caused by mutations affecting the gene represented in this entry. The disease-causing variant may be a homozygous 3-bp deletion in the promoter region of the UFM1 gene, which segregates with the disorder in affected families. In vitro expression studies in different cell lines showed that the mutation significantly reduces transcriptional activity in certain neuronal cell lines (SY5Y and U373), but not in other cell lines, including HeLa and HOF-F2. {ECO:0000269|PubMed:28931644}.

Recessive Scores

• pRec: 0.106

Intolerance Scores

• loftool: 0.617
• rvis_EVS: 0.01
• rvis_percentile_EVS: 54.63

Haploinsufficiency Scores

• pHI: 0.0317
• hipred: N
• hipred_score: 0.230
• ghis: 0.645

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.753

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ufm1

Gene ontology

• Biological process: regulation of intracellular estrogen receptor signaling pathway;response to endoplasmic reticulum stress;negative regulation of apoptotic process;protein ufmylation;protein K69-linked ufmylation
• Cellular component: nucleus;cytoplasm;endoplasmic reticulum
• Molecular function: protein binding