UFC1

protein-coding

ubiquitin-fold modifier conjugating enzyme 1

Gene summary

UFC1 is an E2-like conjugating enzyme for ubiquitin-fold modifier-1 (UFM1; MIM 610553) (Komatsu et al., 2004 [PubMed 15071506]).[supplied by OMIM, Mar 2008]

MANE transcript

NM_016406.4

Inheritance

ClinVar variants

P:2U:33B:5

Top phenotype

Neurodevelopmental disorder with spasticity and poor growth

gnomAD constraint

pLI —, LoF o/e 0.46

Max pathogenic AF

—

Genomic locus

chr1:161,152,776-161,158,856

External References & Databases

Ensembl (ENSG00000143222)

Transcript & Mutation Effects

hg38 • Region Span ~6.1 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

neurodevelopmental disorder with spasticity and poor growthSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0060752

Submitter: PanelApp Australia

neurodevelopmental disorder with spasticity and poor growthSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0060752

Submitter: Labcorp Genetics (formerly Invitae)

neurodevelopmental disorder with spasticity and poor growthDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0060752

Submitter: G2P

neurodevelopmental disorder with spasticity and poor growthLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0060752

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Neurodevelopmental disorder with spasticity and poor growthAR

Manifestation: Craniofacial; Musculoskeletal; 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: 27431290; 29868776

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to UFC1 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 22

Neurodevelopmental disorder with spasticity and poor growthTotal: 9

not providedTotal: 4

UFC1-related disorderTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_016406.4. 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			1 clinvar	4 clinvar		5
missense	1 clinvar	1 clinvar	25 clinvar	1 clinvar		28
nonsense						0
start loss						0
frameshift			2 clinvar			2
splice donor/acceptor (+/-2bp)			5 clinvar			5
Total	1	1	33	5	0	40

Highest pathogenic variant AF is 0.0004423907

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 19 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_016406.4	RefSeq	NP_057490.2	6	MANE Select
ENST00000368003.6	Ensembl	ENSP00000356982.5	6	MANE Select
ENST00000913804.1	Ensembl	ENSP00000583863.1	6	Standard
ENST00000913804.2	Ensembl	ENSP00000583863.1	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

response to endoplasmic reticulum stress
protein ufmylation
protein K69-linked ufmylation

Molecular Function

protein binding
UFM1 transferase activity

Cellular Component

extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000368003
Coding exons: 6
Length: 6081
Individuals with no LoFs: 125736
Homozygous LoFs: 0
Heterozygous LoFs: 12
Defined: 125748
p: 0.0000477

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.234	89	95.4	0.932	0.00000467	1085
Missense (PolyPhen)		39	43.677	0.89292		497
Synonymous	0.269	34	36.1	0.943	0.00000191	311
Loss of Function	1.82	6	13.1	0.458	7.45e-7	123

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000053	0.000053	rare
South Asian	0.000065	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: E2-like enzyme which forms an intermediate with UFM1 via a thioester linkage. {ECO:0000269|PubMed:15071506}.;

Recessive Scores

pRec: 0.130

Intolerance Scores

LoFtool: 0.658
RVIS EVS: -0.34
RVIS percentile EVS: 30.07

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.892

Gene Damage Prediction

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