Table 6.

Notable MCOLN1 Pathogenic Variants

Reference SequencesDNA Nucleotide ChangePredicted Protein ChangeComment [Reference]
NG​_015806 c.-1015_789del6434
(6.4-kb deletion)
--Accounts for 18% of pathogenic variants in Ashkenazi Jewish persons 1
NM_020533​.2 c.406-2A>G--Accounts for 77% of pathogenic variants in Ashkenazi Jewish persons 2
c.694A>Cp.Thr232ProAssoc w/severe phenotype [Manzoni et al 2004]
c.1222_1224delTTCp.Phe408delCauses mildest MLIV phenotype known [Altarescu et al 2002]
c.1084G>Tp.Asp362TyrAssoc w/slower progression of retinal disease & relatively mild neurologic phenotype [Raychowdhury et al 2004]
c.1406A>G 3
(g.9107A>G 4)
p.Asn469SerCauses atypical MLIV, in which affected persons walk independently & have better communicative skills [Altarescu et al 2002]
c.1704A>T 5See footnote 5.
c.1615delGp.Ala539ProfsTer41Assoc w/mildest form of MLIV – isolated retinal degeneration & achlorhydria [Goldin et al 2008]

Variants listed in the table have been provided by the authors. GeneReviews staff have not independently verified the classification of variants.

GeneReviews follows the standard naming conventions of the Human Genome Variation Society (varnomen​ See Quick Reference for an explanation of nomenclature.


Deletion of exons 1 through 5 and part of exon 6; to date, only one individual homozygous for the 6.4-kb deletion has been identified [Bargal et al 2000, Bassi et al 2000, Sun et al 2000].


Approximately 60% of individuals with MLIV of Ashkenazi Jewish heritage in the US are homozygotes for the c.406-2A>G intronic acceptor splice site pathogenic variant. An estimated 33% are compound heterozygotes for this variant and the 6.4-kb deletion [Wang et al 2001, Goldin et al 2004a].


Base pair transition creates a new preferred splice acceptor site that results in a frameshift.


Variant designation that does not conform to current naming conventions


Near the donor site of intron 13; creates an alternative donor splice site that results in a frameshift [Dobrovolny et al 2007].

From: Mucolipidosis IV

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